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Indian Journal of Clinical Biochemistry logoLink to Indian Journal of Clinical Biochemistry
. 2024 Feb 17;40(3):455–466. doi: 10.1007/s12291-024-01191-2

Spirulina Platensis Alleviates γ- Radiation-Induced Brain Damage by Attenuating Oxidative Stress and Increasing Brain-Derived Neurotrophic Factor (BDNF) Levels in Male Albino Rats

R M Ebrahim 1, Ahmed Hammad 2,✉, Hebatallah E Mohamed 2
PMCID: PMC12229397  PMID: 40625612

Abstract

Ionizing radiation can irreversibly damage the brain cells’ function and structure. Spirulina platensis (Sp) is widely employed as a dietary supplement because it has anti-inflammatory, antioxidant, and immunomodulating properties. Therefore, this work aims to investigate the protective properties of Sp towards γ-irradiation (IRR)-induced brain damage. The whole-body male albino rats were exposed to IRR with a 7 Gy single dose in the absence or presence of Sp (400 mg/kg body weight). The rats were divided into four groups: Group I (control), Group II (Sp), Group III (IRR), and Group IV (Sp + IRR + Sp). The biochemical and histopathological investigations were evaluated two weeks post-irradiation. The results showed that irradiation increased inflammation by increasing tumor necrosis factor-alpha (TNFα), IL-1B, and IL-6 while decreasing IL-10. Additionally, irradiation evoked nucleic acid damage. Furthermore, IRR provoked oxidative stress. Similarly, the IRR caused neurotransmitter disturbances by increasing S100 calcium-binding protein (S100B) and γ- aminobutyric acid (GABA) levels while reducing brain-derived neurotrophic factor (BDNF) and glutamate levels in brain tissue. Therefore, Sp alleviated IRR-induced brain damage by attenuating the above-mentioned parameters and ameliorating histopathological changes. Consequently, it could be concluded that Sp might exert a beneficial effect on irradiation-induced brain damage by attenuating oxidative stress, regulating BDNF, and suppressing S100B.

Keywords: Spirulina Platensis, Oxidative Stress, γ-irradiation, Brain, BDNF, S100B

Introduction

Although radiation is widely regarded as a valuable therapeutic and diagnostic tool, it is typically hazardous to various body tissues, particularly the brain, when administered in elevated doses [1, 2]. This adverse impact is caused by either the direct ionization of cellular components, particularly DNA, or the indirect harm caused by free radicals generated by water radiolysis [3, 4]. Previous research demonstrated that 7 Gy of whole-body irradiation caused brain damage by impairing mitochondrial brain function [5]. In addition, 20 Gy (a single dose) of cranial irradiation caused oxidative stress in the blood and brain tissue [6]. Moreover, 10 Gy of head irradiation caused DNA injury, accompanied by a substantial rise in inflammatory and apoptotic indicators, with a noticeable reduction in brain tissue neurotransmitter levels [7]. In addition, BDNF and S100B are known to have a significant impact on the development of the nervous system and may be involved in the development of neuropsychiatric disorders [8].

BDNF is an essential neurotrophic factor for neuronal survival and neuroplasticity [9]. In the hippocampus and frontal cortex, BDNF promotes neuroregeneration, neurogenesis, neuroprotection, synaptic plasticity, cell survival, and memory retention, formation, and recall [10]. Moreover, BDNF controls inflammatory homeostasis through the hedgehog and erythropoietin signaling pathways, thereby reducing inflammation [11]. S100B is a calcium-binding peptide predominantly generated and released in the brain by astrocytes; however, this protein participates in multiple intracellular and extracellular processes [12]. The effects of S100B on glial cells and neurons in the extracellular space depend on its content [13]. Additionally, S100B has been proposed as an astrocyte-mediated regulator of neuronal synaptic plasticity [14]; however, Its secretion is influenced by many secretagogues, such as neurotransmitters and cytokines, including dopamine and glutamate [15]. GABA is one of the most common neurotransmitters in mammals and an essential inhibitory neurotransmitter of the central nervous system (CNS); however, it accumulates in most brain regions and is involved in 40% of the inhibitory synapses of adult mammals [16]. Moreover, It is generated in the CNS via the decarboxylation of glutamic acid catalyzed by glutamic acid decarboxylase (GAD). Additionally, GABA performs its inhibitory action via two distinct receptor classes, GABAB (metabotropic) and GABAA (ionotropic), which exhibit distinct pharmacological, structural, and molecular divergences [17].

Furthermore, several hypotheses have been postulated for unraveling the pathophysiology of radiation-induced brain injury, including immunoinflammatory responses, radiation-induced direct lesions, and oxidative stress [18, 19]. Thus, many experimental investigations have indicated in recent years that strategies such as controlling inflammation and minimizing oxidative stress might ameliorate or prevent radiation-induced brain damage [20].

Spirulina is a fibrous cyanobacterium that thrives in alkaline water. However, it is widely used as a dietary nutritional ingredient throughout the globe since it has a large number of beneficial substances, including phenols, phycocyanins, and polysaccharides [20]. In addition, Spirulina species contain a high concentration of proteins, minerals, vitamins, essential fatty acids, carotenoids, glycolipids, and essential amino acids; consequently, they are frequently consumed as nutritional supplements that enhance people’s health, as well as mental and physical efficiency. In addition, the nutrients in Spirulina are readily assimilated by the body and quickly return nutritional deficiencies to physiologic amounts. Thus, the elevated bioavailability properties of micronutrients enable their quick uptake in the nervous system [21]. Additionally, Spirulina has in vitro and in vivo anti-inflammatory, antioxidant, and immunomodulatory properties [21]. On the other hand, recent studies have discovered Spirulina’s neuroprotective effect on the maturation of the nervous system, senescence, and various illnesses, including neurodegenerative and neurological diseases [20], through lowering oxidative stress and possessing antioxidant capacities [22]. However, it is attributed to high phycocyanobilin levels, an inhibitor of NADPH oxidase, which may be linked to oxidative stress in several neurodegenerative disorders [23]. In light of this, the purpose of the current work is to assess the ameliorative impact of Spirulina platensis on male albino rat brain injuries caused by exposure to radiation.

Materials and Methods

Animals

The National Center for Radiation Research and Technology (NCRRT) breeding unit in Cairo, Egypt, offered male Wistar albino rats (12 ± 2 weeks old; 200 ± 10 g). Before beginning the investigation, animals were acclimated to the laboratory environment for at least a week. The rats were housed in standard light, temperature, ventilation, and humidity; however, they had unfettered access to an ordinary diet with all the essential nutrients. Nonetheless, food and water were accessible for free choice during the experiments. The experiments were conducted in accordance with the regulations and rules of the Research Ethics Committee of the National Centre for Radiation Research and Technology (REC- NCRRT). REC has approved the research protocol, following the 3Rs Principles for animal experimentation (Replace, Reduce, and Refine), which is organized and operated according to the CIOMS and ICLAS International Guiding Principles for Biomedical Research involving Animals 2012. Centre and the guidelines for the correct handling and use of laboratory animals released by the National Institutes of Health (HIN publication No. 85–23, updated 1985) under worldwide ethical standards. In addition, the Central Scientific Publishing Committee of the Atomic Energy Authority (Egypt) approved the study, Rf. (203)-10/3/2021. In addition, the Central Scientific Publishing Committee of the Atomic Energy Authority approved the study, Ref. (22A)-28/2/2023.

Chemicals

All used reagents, kits, and chemicals were bought from Sigma-Aldrich in St. Louis, Missouri, United States. Spirulina platensis was obtained from the Malaysia (DXN) company.

Experimental Design

The animals were randomly grouped into four distinct categories (n = 6): Group I (control), Group II (Sp), Group III (IRR), and Group IV (Sp + IRR + Sp). In the control (CTRL) group, rats received distilled water by gavage for 14 days. In Sp, the rats received 400 mg/kg body weight (b.w) suspended in distilled water daily via gavage for 14 days [24]. In IRR, rats (whole-body) were subjected to γ-irradiation (7 Gy, single dose). Prior experiments on rats have demonstrated that exposing the entire body to radiation at a dose of 7 Gy leads to brain damage [5]. In Sp + IRR + Sp, the rats received Sp (400 mg/kg b.w) for seven days orally, then were subjected to 7 Gy γ-radiation (single dose), and then the rat was continuously received Sp (400 mg/kg b.w) for another seven days orally after 2 h of irradiation.

Irradiation Procedure

The IRR procedure was performed at the NCRRT utilizing a Canadian Gamma Cell-40 (137Cs). The animals were subjected to a single radiation dose (7 Gy) at a 0.48 Gy/min dose rate.

Determination of the Body Weight

The rat body weights in all groups were determined before and after the experimental period.

Sample Collection and Preparation

After overnight fasting, animals were anesthetized with urethane and subsequently sacrificed. However, the blood specimens were gathered by puncturing the heart. Subsequently, the serum was isolated by 3000 rpm centrifugation and kept at − 20 °C until analyses. The brain’s cerebral cortex was taken out, and 10% (weight/volume) of tissue homogenates were performed in ice-cold 0.1 M phosphate buffer (pH 7.4). Afterward, the homogenate of brain tissues was centrifuged, and the supernatant was taken out for additional biochemical examination. Meanwhile, a portion of brain tissue was fixated in a 10% buffered formalin solution in preparation for the histopathological assessment.

Biochemical Examinations

Oxidative Stress Assessment

Yoshioka et al. [25] demonstrated a method for quantifying MDA content in tissue homogenates to determine lipid peroxidation. However, this method relies on measuring the concentration of malondialdehyde (MDA), a byproduct of lipid peroxidation. MDA can react with thiobarbituric acid in acidic conditions to produce a pink-colored trimethine complex that absorbs light at a maximum wavelength of 532 nm. In addition, a methodology was developed by Minami and Yoshikawa [26] to evaluate the SOD activity in tissue homogenates. Briefly, the mixture was subjected to centrifugation at a speed of 2500 rpm for a duration of 15 min at a temperature of 4 °C. The 0.25 ml of supernatant was combined with 0.5 ml of tris cacodylic buffer, along with 0.1 ml of 16% triton x-100 and 0.25 ml of nitroblue tetrazolium. The reaction was initiated by introducing 0.01 ml of diluted pyrogallol. The sample was incubated for 5 min at a temperature of 37 °C. The reaction was halted by introducing 0.3 ml of a 2 M formic acid solution. The spectrophotometric determination was used to measure the generated formazan color. In accordance with Miller et al. [27], the TAC of brain tissue was determined using a Randox total antioxidant status assay (UK). The compound 2,2′ azino-di-(3-ethylbenzothiazoline sulphonate was combined with a peroxidase (metmyoglobin), hydrogen peroxide, and the sample. This mixture produced the radical cation, which can be detected by its blue-green color at a wavelength of 600 nm. For an assessment of protein oxidation, the PCO was measured based on the procedure of Levine et al. [28], employing assay Kit Cat. No. MAK094 (Sigma Aldrich, St. Louis, Missouri). The PCO group undergoes a reaction with 2,4-dinitrophenylhydrazine (DNPH) to produce chromophoric dinitrophenylhydrazones. Following the DNPH reaction, DNPH was dissolved in HCl. Proteins, on the other hand, were precipitated using an equal volume of 20% (w/v) trichloroacetic acid. The precipitated proteins were then washed three times with 4 mL of a mixture containing equal parts ethanol and ethyl acetate (1:1). The resulting precipitates were dissolved in a solution of guanidine HCl at a concentration of 6 M, and the absorbance was measured at a wavelength of 370 nm. The quantity was displayed as nmol/gm of fresh tissue.

Evaluation of Brain DNA and RNA Content

The levels of DNA were measured by quantifying nucleic acids according to the reaction of diphenylamine solution with sugar parts. The amount of RNA was estimated based on the reaction between its sugar part and the orcinol agent [29–31].

Determination of Neurotransmitters

BDNF was determined using the K-Assay ELISA kits (Cat. No. KT-8575) in rat brain tissue homogenates. Briefly, tissues were rinsed in ice-cold PBS (0.01 mol/L, pH 7.0) to remove excess blood thoroughly and weighed before homogenization. Subsequently, the tissues were minced into small pieces and homogenized in 5 ml of PBS with a glass homogenizer on ice. The resulting suspension was subjected to two freeze–thaw cycles to break the cell membranes further. Then, the homogenates were centrifuged for 5 min at 500 xg. The supernatants were collected. Furthermore, the BDNF level (ng/ml) was determined according to the described protocol.

Additionally, S100-B was examined by the MyBioSource ELISA kits in brain tissues of different rat groups with RIBA lysing buffer (Cat. No. MBS2090451), according to the manufacturer’s instructions. Glutamic acid and GABA levels were determined in brain tissues homogenate using the MyBio Source competitive ELISA technique (Cat No. MBS7212767) (Inc. USA).

Inflammatory Marker Examinations

IL-1β, IL-10, and IL-6 contents were evaluated in the supernatant of brain homogenates via ELISA kits (Cat. No. MBS825017, Cat. No. MBS269892, and Cat. No. MBS034393, respectively), with the manufacturer’s guidelines (MyBioSource, Inc. USA). Using Rat TNF-α ELISA kits (Cat. No. MBS355371), the level of tumor necrosis factor- (TNF-α) was determined as per the manufacturer’s specifications.

Histopathological Examinations

Brain tissue samples were obtained, sliced, and fixated in a formalin solution (10%). A series of dehydration, clarifying, and embedding procedures were conducted. Subsequently, paraffin blocks were made from these samples. The paraffin-embedded specimen was sliced to a 4 to 5 µm thickness utilizing a microtome, placed on microscope slides, and stained with eosin and hematoxylin [32]. The specimen was next inspected with a light microscope to assess the alterations.

Statistical Analysis

The findings were assessed statistically through version 20 of the SPSS computer program. All data were displayed as Mean ± SD. A one-way ANOVA followed by a post hoc the least significant difference (LSD) was utilized to compare the groups. P < 0.05 stated that the changes were significant.

Results

Spirulina Platensis (Sp) Improved Radiation-induced Weight Loss

Results in this study displayed a non-significant change in b.w after treating rats with Sp for 14 days in the Sp group relative to the control one. Whereas irradiation caused a significant decrease in b.w after 14 days post-irradiation in the IRR relative to the control. Nevertheless, treating irradiated animals with Sp pronounced improved the rat b.w in the Sp + IRR + Sp group with respect to the IRR group (Fig. 1).

Fig. 1.

Fig. 1

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Effect of Sp on radiation-induced weight loss in rats. The bar chart shows that radiation decreased rat body weight in the IRR rats in regard to the control [CTRL] rats, whereas Sp increased the body weight in the Sp + IRR + Sp group in comparison to the IRR rats. (Mean ± SD; n = 6; ns p-value > 0.05, **p-value < 0.01, and ****p-value < 0.0001)

Spirulina Platensis (Sp) Improved Radiation-induced Brain Oxidative Stress

Irradiation triggered oxidative stress in the cerebral cortex, as evidenced by decreasing TAC levels and SOD activity, with increasing protein carbonyl (PCO) and malondialdehyde (MDA) levels in the IRR rats compared to the CTRL rats (Fig. 2). However, treating the irradiated rats with Sp improved oxidative stress by increasing TAC levels and SOD activity and decreasing MDA and PCO levels in the Sp + IRR + Sp relative to the IRR (Fig. 2). Meanwhile, Sp treatment of non-irradiated rats did not cause any significant alteration in all oxidative stress parameters measured in this study (Fig. 2).

Fig. 2.

Fig. 2

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Effect of Sp on radiation-induced oxidative stress in the brain of rats. a The bar chart shows that the radiation increased the MDA level in the IRR relative to the CTRL, while Sp significantly decreased the MDA level in the Sp + IRR + Sp group regarding the IRR group. b A bar chart shows that radiation reduced the SOD activity in the IRR with respect to the CTRL, while Sp significantly increased the SOD activity in the Sp + IRR relative to the IRR. c The bar chart shows that radiation increased the PCO level in the IRR relative to the CTRL, while Sp significantly decreased the PCO level in the Sp + IRR + Sp relative to the IRR. d A bar chart shows that radiation reduced the TAC levels in the IRR relative to the CTRL, while Sp significantly increased the TAC level in the Sp + IRR + Sp group relative to IRR group. (Mean ± SD; n = 6; ns p-value > 0.05, *p-value < 0.05, ***p-value < 0.001, and ****p-value < 0.0001)

Spirulina Platensis Improved Radiation-induced Brain Nucleic Acid Damage

Irradiation induced nucleic acid damage in the cerebral cortex by significantly decreasing the DNA and RNA contents of irradiated rats relative to control rats. Therapy of irradiated rodents with Sp significantly improved genetic material damage in the cerebral cortex by significantly increasing DNA and RNA content in the Sp + IRR + Sp group relative to the IRR. Meanwhile, Sp therapy in non-irradiated rodents did not induce significant changes in DNA and RNA levels (Fig. 3).

Fig. 3.

Fig. 3

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Effect of Sp on radiation-induced genetic material damage in the brain of rats. a The bar chart shows that radiation significantly decreased the DNA level in the IRR relative to the CTRL, while Sp significantly increased the DNA level in the Sp + IRR + Sp relative to the IRR. b The bar chart shows that radiation significantly decreased the RNA level in the IRR relative to the CTRL, while Sp significantly increased the RNA level in the Sp + IRR + Sp relative to the IRR. (Mean ± SD; n = 6; ****p-value < 0.0001)

Spirulina Platensis Improved Radiation-induced Brain Neurotransmitter Disturbances

Furthermore, γ-irradiation evoked a marked variation in the neurotransmitter contents in the cerebral cortex. Particularly, the S100B was remarkably raised in the IRR in comparison to the CTRL, whereas the BDNF was significantly reduced in the IRR with respect to the CTRL. Additionally, irradiation significantly reduced the excitatory neurotransmitter glutamic acid (GLU) and increased gamma amino butyric acid (GABA) in the IRR with respect to their respective values in the CTRL. Surprisingly, Sp treatment improved the neurotransmitter variations in the cerebral cortex, which was evidenced by significantly ameliorating the S100B levels and increasing the BDNF levels, as well as increasing glutamic acid and decreasing GABA in the treated group with respect to the IRR group (Fig. 4). Meanwhile, Sp in non-irradiated rats did not induce any significant change in neurotransmitter levels (Fig. 4).

Fig. 4.

Fig. 4

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Impact of Sp on radiation-induced neurotransmitter disturbances in the brains of rats. a A bar chart shows that radiation increased the S100B level in the IRR relative to the CTRL, whereas Sp significantly decreased the S100B level in the Sp + IRR + Sp relative to the IRR. b The bar chart shows that radiation reduced the BDNF level in the IRR with respect to the CTRL group, while Sp significantly increased the BDNF level in the Sp + IRR + Sp relative to the IRR. c A bar chart shows radiation increased the GABA level in the IRR with respect to the CTRL, while Sp significantly decreased the GABA level in the Sp + IRR + Sp relative to the IRR. d A bar chart shows that radiation reduced the glutamate level in the IRR relative to the CTRL, while Sp significantly increased the glutamate level in the Sp + IRR + Sp group in comparison to the IRR group. (mean ± SD; n = 6; ns p-value > 0.05, *p-value < 0.05, **p-value < 0.01, ***p-value < 0.001, and ****p-value < 0.0001)

Spirulina Platensis Improved Radiation-induced Brain Inflammation

On the other side, the findings in the current research displayed that γ-irradiation caused inflammation in the cerebral cortex. This inflammation was evidenced by markedly increasing the proinflammatory cytokine marker levels, including tumor necrosis factor-alpha (TNF-α), IL-IB, and IL-6, post-irradiation relative to their respective values in the untreated rats, whereas significantly decreasing contents in the anti-inflammatory marker IL-10 post-irradiation in comparison to their values in the control. Notably, Sp ameliorated the radiation-induced inflammation by decreasing the proinflammatory cytokine marker levels, including tumor necrosis factor-alpha (TNF-α), IL-IB, and IL-6, as well as increasing the level of the anti-inflammatory marker IL-10 in the treated group in comparison to their values in the irradiated group (Fig. 5). Meanwhile, Sp treatment of non-irradiated rats did not induce any significant change in inflammatory cytokine marker levels (Fig. 5).

Fig. 5.

Fig. 5

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The impact of Sp on radiation-induced inflammation in the brain of rats. a A bar chart shows that radiation increased the TNFα level in the IRR with respect to the CTRL, whereas Sp significantly decreased the TNFα level in the Sp + IRR + Sp group with respect to the IRR. b The bar chart shows that radiation elevated the IL-6 level in the IRR relative to the CTRL, while Sp significantly decreased the IL-6 level in the Sp + IRR + Sp relative IRR. c A bar chart shows that radiation increased the IL-1B level in the IRR group in comparison to the CTRL group, while Sp significantly decreased the IL-1B level in the Sp + IRR + Sp group compared to the IRR group. d A bar chart shows that radiation reduced the IL-10 level in the IRR with respect to the CTRL, while Sp significantly increased the IL-10 level in the Sp + IRR + Sp group compared to IRR group. (mean ± SD; n = 6; ns p-value > 0.05, ***p-value < 0.001, and ****p-value < 0.0001)

Spirulina Platensis Improved Radiation-induced Brain Histopathological Damages

Finally, histopathological examination results indicated that irradiation caused histopathological injury in the cerebral cortex of male albino rats. The cerebral gray matter of rats in the control group exhibited a normal histological structure (Fig. 6a). Similarly, the cerebrum white matter in Sp group showed a normal structure (Fig. 6b). In the IRR group, the neuronophagia and degenerative alterations of the brain are not severe, which were exhibited in various regions of the brain, particularly the cerebrum, of all rodents examined, and were exemplified by numerous pyknotic neurons with the glial cell proliferation in gray matter (Fig. 6c, d, e, and f). In the Sp + IRR + Sp group, the gray matter of some rodents displayed a little degenerated pyramidal neurons (Fig. 6g), but the matrix and neurons showed a normal morphological image for the white matter of the rat treated with the Sp and γ-irradiated group (Fig. 6h).

Fig. 6.

Fig. 6

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The effect of Spirulina platensis on radiation-induced histopathological damages in the brain of male Albino rats. a The gray matter of the control rodent shows a normal structure (H &E × 400). b The white matter of the treated rat shows a normal structure (H&E × 400). c The gray matter of the IRR shows pyknosis and perineural vacuolation of pyramidal neurons (H&E × 400). d The white matter of irradiated rats shows satellitosis and increasing microglial spongiform degeneration (H &E × 400). e The gray matter of irradiated rats shows degenerated pyramidal cells, severely congested blood vessels, and increasing neuroglia cells (H &E × 400). f The white matter of irradiated rats shows hemorrhage and microcavitation (H &E × 400). g The gray matter of the Sp + IRR + Sp group shows little degenerative change in neuronal cells (H &E × 400). h A white matter of the Sp + IRR + Sp group shows a slight microglia cluster (H &E × 400)

Discussion

Spirulina platensis is a cyanobacterium with an elevated protein level, presenting a neuroprotective impact [33]. Sp enhances motor and cognitive abilities and inhibits endothelial rupture in the brain. Sp has demonstrated anti-inflammatory and antioxidant properties by lowering free radicals and oxidative stress [34]. Several animal and human investigations have documented the potential advantageous benefits of Spirulina platensis in relation to numerous disorders, including diabetes [35], dyslipidemia [36], and chronic obstructive pulmonary diseases [37]. According to reports, the reduction in oxidative stress and the inflammatory process generally had positive benefits [38].

Moreover, Sp has shown good outcomes in an exercise context, as well as in therapeutic settings [39]. Athletes in India have been consuming S. platensis as part of their training regimen for track and field events [40]. The Chinese and Cuban Olympic teams incorporate Sp into their daily diet as part of their training regimen [41]. The study indicates that there is a correlation between the consumption of Sp and improvements in strength and exercise performance in humans [40]. Thus, the current research investigated the impact of Sp on radiation-induced brain damage.

Radiation’s primary mechanism of toxicity in healthy cells is the induction of oxidative stress, which might result in cell death [42–44]. Thus, the popular indicators of oxidative stress were utilized to figure out the impact of Sp on radiation-evoked brain damage, including MDA, TAC, SOD, and PCO. The results of the current work displayed that irradiation caused oxidative stress by significantly lowering TAC levels and SOD activities, with a marked increase in MDA and PCO levels. These results have coincided with previous findings that showed the irradiation caused oxidative stress in the brain, as evidenced by a substantial rise in PCO, MDA, and 8-hydroxy-2-deoxyguanosine, which are indicators of protein, lipid, and DNA oxidation, respectively [1]. The findings suggest that radiation may cause brain alterations through free radicals that diffuse and damage the brain [1, 3, 4].

On the other hand, Sp treatment ameliorated the oxidative stress condition through increasing TAC levels and SOD activities, with a marked decrease in MDA and PCO levels; however, these findings coincide with those of Saad-El-Din et al. [45], who exhibited that Sp ameliorated brain tissue oxidative stress through SOD activity elevation and PCO level reduction. In addition, Sp ameliorated brain tissue oxidative stress through TAC level elevation and MDA level reduction [34]. Mechanistically, Sp’s free radical-scavenging and antioxidant properties can be ascribed to its bioactive contents, including phycocyanin [46], allophycocyanin [47], carotene, vitamins, chlorophyll, α-lipoic acid, SOD enzyme, selenium, riboflavin, magnesium, carotenoid [34], polysaccharides, and manganese [48, 49].

In addition, radiation increased IL-6, IL-1β, and TNF-α contents and reduced the IL-10 content of the IRR group relative to the control group. However, these outcomes coincide with Algeda et al. [2] and Hammad et al. [1]. Ionizing radiation primarily triggers inflammatory responses in the brain by activating microglia and endothelial cells [50], which in turn stimulate the NFκB pathway-mediated synthesis of inflammatory proteins [51]. Sp treatment alleviated brain neuroinflammation attributed to its anti-inflammatory properties by inhibiting inflammatory mediator expression, such as inducible nitric oxide synthase, cyclooxygenase-2, IL-1, TNF-α, and IL-6, through in vitro and in vivo inflammation models [38, 52]. Moreover, previous studies explored that Sp treatment ameliorated IL-1β, IL-10, IL-6, and TNF-α levels [38, 53]. Thus, Spirulina could induce an anti-inflammatory impact through its active compounds, including phycocyanobilin, phycocyanin, and β-carotene, all of which exhibit promising anti-inflammatory activity [38]. β-carotene defends against singlet oxygen-mediated lipid peroxidation, limits internal ROS buildup, and suppresses inflammatory gene expression [54]. Additionally, Spirulina modulates the p38, JNK, ERK1/2, and IB signaling pathways, resulting in anti-inflammatory and antioxidant benefits [55, 56]. Phycocyanin eliminates free radicals, blocks lipid peroxidation, and diminishes iNOS expression and nitrite formation [38].

The biggest impacts of oxidative stress are DNA damage; however, studies have indicated that the brain is vulnerable to oxidative stress [2, 57]. In the current work, ionizing radiation increased the DNA and RNA contents of the IRR relative to the CTRL. Sp treatment exerts a protective effect against DNA damage and oxidative stress. Thus, Sp ameliorated the DNA and RNA levels in the Sp + IRR + Sp group relative to the IRR. These findings agree with a previous study by Alam and Hendawi [58]. Sp significantly decreased the degree of DNA fragmentation in the brain cells; thus, it reduced the pathological damage to the brain tissue [58]. Thus, Spirulina could protect against oxidative stress by averting DNA breakdown, possibly through scavenging free radicals and boosting the activity of CAT and SOD [38].

Additionally, irradiation evoked a sustainable variation in the neurotransmitter contents in the cerebral cortex. In particular, radiation increased S100B and GABA contents and decreased BDNF and glutamic acid contents. However, these findings agree with previous results showing that whole-body irradiation changed neurotransmitters’ levels [1, 2]. MDA can react with primary amines on peptides to create crosslinks and interact with nucleic acid bases to produce numerous adducts [59]. The decline in BDNF and glutamic acid indicates that exposure to radiation may result in the degeneration of neurotransmitters [1]. The substantial changes in brain neurotransmitters in irradiated rats may be attributable to the elevated rate of generation of H2O2 and O2•− in the brain tissues, which may cause neurodegenerative conditions and Lewy body aggregations [60]. Oxidative stress substantially altered electrolyte contents, which likely displayed a substantial reduction in all neurotransmitter levels examined [61]. The GABA concentrations in the brain and colon of rodents exposed to radiation significantly increased relative to the control [62]. In addition, radiation increased the surface expression of inhibitory gamma-aminobutyric acid receptors [63]. Although GABA serves a crucial role in the physiology of the CNS by modulating various processes, it is also implicated in several pathologies and serves as a target for several therapies [64]. Furthermore, ionizing radiation could affect neurotransmitters’ concentration by boosting their catabolism, inhibiting or triggering their release, reducing their synthesis rate, prohibiting their retention in synaptic vesicles, and impeding their attachment to receptors [2]. S100B is an intriguing biomarker for outcome prediction following traumatic brain injury [65]. Elevated levels of the S-100B protein appear to be linked to radiation-induced brain damage [66].

On the other side, Sp therapy improved radiation-induced brain neurotransmitter disturbances. Sp improved BDNF levels in LPS-induced brain inflammation, possibly via normalizing effects on phosphorylated AKT (pAKT) [67]. Additionally, Sp might improve brain damage by inhibiting glycogen synthase kinase-3 phosphorylation, decreasing glutathione levels, and activating the BDNF/phosphatidylinositol-3 kinase/serine/threonine-protein kinase signaling pathway [68]. The BDNF signaling cascade modulates neuroinflammatory processes by regulating endogenous cross-talk between microglia and astrocytes [11]. Additionally, the expression of cyclooxygenase-2 and proinflammatory cytokines in microglia could be downregulated by BDNF, thereby influencing the inflammatory response [69]. The reduced activity of multiple pathways, such as the NF-κB pathway, may be responsible for the ameliorating effects of BDNF overexpression on neuroinflammation and synaptic dysfunction in the hippocampus [69]. Moreover, an important aspect of Sp’s role in neuroprotection is due to the inhibition of radical formation through its anti-inflammatory effects [58]. On the other hand, Sp treatment normalized the decrease in BDNF and glutamate levels and significantly improved S100B and GABA levels. Surprisingly, these results agree with previous studies that showed Sp treatment improved neurotransmitter alterations [58, 70].

Conclusion

Sp alleviated gamma irradiation-induced brain damage by attenuating oxidative stress and inflammation; in addition, Sp ameliorated neurotransmitter alteration in the brain. Moreover, Sp improved radiation-induced brain genetic material damage. Thus, it is capable of reducing pathological damage to brain tissue.

Declarations

Conflict of interest

The authors declare that they have no competing interests.

Ethics approval

The experiments were conducted in accordance with the regulations and rules of the Research Ethics Committee of the National Centre for Radiation Research and Technology (REC- NCRRT).

Informed consent

Not applicable.

Footnotes

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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