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. Author manuscript; available in PMC: 2024 Jul 15.
Published in final edited form as: J Neurol Sci. 2023 May 2;450:120663. doi: 10.1016/j.jns.2023.120663

Elevated Brain Derived Neurotrophic Factor in Plasma and Interleukin-6 levels in Cerebrospinal Fluid in Meningitis Compared to Cerebral Malaria

Monique F Stins 1,2,*, Agnes Mtaja 3, Evan Mulendele 3, Daniel W Mwimbe 3, Gabriel Pinilla 4,5, Mable Mutengo 3,6, Carlos A Pardo 4, James Chipeta 3,#
PMCID: PMC10330544  NIHMSID: NIHMS1900698  PMID: 37182424

Abstract

Neurological infections, such as Cerebral malaria (CM) and meningitis are associated with high mortality and in survivors, particularly young children, persistent neurologic deficits often remain. As brain inflammation plays a role in the development of these neurological sequelae, multiplex assays were used to assess a select set of immune mediators in both plasma and cerebrospinal fluid (CSF) from Zambian children with neurological infections.

Both CM and meningitis patients showed high levels of markers for vascular inflammation, such as soluble ICAM-1 and angiopoietins. Although high levels of angiopoietin 1 and angiopoietin 2 were found in the meningitis group, their levels in the CSF were low and did not differ.

As expected, there were high levels of cytokines and notably a significantly elevated IL-6 level in the CSF of the meningitis group. Interestingly, although elevated levels BDNF were found, BDNF levels were significantly higher in plasma of the meningitis group but similar in the CSF. The striking differences in plasma BDNF and IL-6 levels in the CSF point to markedly different neuro-pathological processes. Therefore, further investigations in the role of both IL-6 and BDNF in the neurological outcomes are needed.

Keywords: Brain-Derived-Neurotrophic -Factor, Interleukin-6, Cerebral Malaria, meningitis, inflammation, Plasmodium

Graphical Abstract

High BDNF and IL-6 responses in meningitis versus cerebral malaria.

Shown is blood compartment (bottom) and brain compartment (upper section) separated by brain endothelial cells of the blood brain barrier. In brain inflammation, the main BDNF production shifts from neurons and brain endothelial cells to astrocytes. Activated microglia release high levels of IL-6, especially in meningitis. As a result of exposure to Plasmodium infected red blood cells versus bacteria, virus and their toxic products, inflammation of the brain endothelial cells leads to a differential release of cytokines, Angiopoietins, s-ICAM-1 and BDNF into the circulation. In addition, activated immune cells and platelets contribute to BDNF levels in plasma, resulting in higher BDNF levels in meningitis, compared to cerebral malaria.

graphic file with name nihms-1900698-f0001.jpg

1. INTRODUCTION

Cerebral malaria (CM) is a clinical syndrome associated with Plasmodium falciparum infection with high mortality of up to 30%, particularly in children and persistent neurologic deficits remain in CM survivors 1, 2. However, the underlying pathogenic mechanisms associated with long-term outcomes of CM are unclear (see a review Schiess et. al. 3). In contrast to numerous other neuro-pathogens, in CM, the Plasmodium infected red blood cells (PRBC) do not cross the blood-brain barrier (BBB) into the central nervous system (CNS) but sequester intravascularly in cerebral blood vessels. Therefore, it has been speculated that PRBC-induced microvascular inflammation significantly contributes to the neuropathogenesis in CM. In addition to producing cytokine disturbances, neuronal growth factor networks are disrupted in CM 4. This may include brain derived nerve growth factor (BDNF), a neurotrophin secreted by brain endothelial cells 5 and a critical factor involved in neuronal plasticity, learning, and memory organization 6, 7. BDNF-mediated neuronal repair may be specifically impacted in CM leading to post-CM neurologic sequelae. Although several studies have reported on select plasma cytokines in CM and severe malaria in plasma 8–11, there is very limited information on the profile of cytokines in the CSF. Because of their critical roles, an altered balance of cytokines and growth factors in neurological infections could contribute significantly to the observed neurological sequelae in CM 12. Therefore, our study focused on assessing select inflammatory markers, including sICAM and angiopoietins and the growth factor BDNF in plasma and CSF obtained from subjects with CM and meningitis.

2. MATERIAL AND METHODS

2.1. Demographics and clinical information.

Children aged between 6 months to 15 years presenting with acute symptoms of CM were enrolled in the study. Control subjects, the meningitis diagnosis group, were patients with acute neurological symptoms associated with viral or bacterial meningitis. Patients were screened for HIV and only those who tested negative were included in the study. Participants for this study were recruited from the pediatric ward of the University Teaching Hospital, Lusaka, Zambia. After receiving the consent of parents or legal guardians, clinical and paraclinical parameters including vital signs, temperature, and a pediatric Glasgow Coma were recorded.

2.2. Collection of biological samples.

Blood samples were collected aseptically (EDTA vacumax) by venipuncture from each recruited child for standard diagnostics (malaria parasitemia, cell blood count, glucose) and for blood culture (bottle containers, Bactech ®) to rule out bacteremia. The remainder of the blood samples were centrifuged at 3500g and aliquots of plasma were stored at −80°C until further analysis was conducted. CSF was aseptically collected by lumbar puncture. After standard-of-care diagnostic studies, which included microbiological studies to investigate for meningitis, CSF was centrifuged to remove cells and aliquots of the supernatant were stored at −80°C until further analysis of cytokines and BDNF.

2.3. Determination of plasma and CSF analytes.

The determination of selected cytokine and chemokine concentrations in plasma and CSF was done using multiplexed microbead array assays (Magpix, Millipore®) according to the manufacturer’s instructions. Kit HCYTOMAG60K was used for the indicated cytokines and HND3MAG-36K for BDNF and s-ICAM-1. Kits were run on an 40–072 MAGPIX® instrument with xPONENT® 4.2 MAGPIX® analyser software.

2.4. Statistical analysis and graphing.

Statistical analysis was performed using Stata, version 14 (Stata Corp, College Station, TX, USA). Data are presented as medians with interquartile ranges (IQR) based on the number of observations and a probability distribution. Comparisons of serum and CSF concentrations were performed using Mann-Whitney’s U statistic. Categorical variables were analyzed through χ2 or Fisher’s exact test according to the number of subjects within each cell of the contingency table. The Spearman’s rank coefficient was used to determine the correlation between the analyte concentration and haematological laboratories results (RBC, haematocrit, and platelets). Graphs were drawn using GraphPad Prism, version 7.02 (GraphPad Software, La Jolla, CA, USA). A graphic abstract was made using Biorender (Biorender.com).

2.5. Participants and ethical approvals.

All research was in accordance with the Helsinki Declaration and approved by both the Johns Hopkins and Zambian Eres Converge IRBs. Informed consent to participate in the study was obtained from the participant’s parents or legal guardians for children under 16.

3. RESULTS and DISCUSSION

3.1. Demographics and clinical features:

A description of the study population, demographics and clinical features are as follows: the median age of the participants was 4 years (IQR 3.1–4.9) for the CM group and 2.5 years (IQR 2–9) for the meningitis group. The weight average was 16 kg (IQR 13–20) and 12 kg (IQR 8.6–26.5) for the CM and meningitis group respectively. No statistical differences were found for the median temperature of the patients (38.8 °C, IQR 37.7–39.9 °C) upon admission.

Differences observed were in the pediatric Glasgow coma score, which was 8 (IQR 8–9) for the CM group and 10 (IQR 9–15) for the meningitis group. The RBC volume and platelets differed between these groups, respectively (3.5 106 RBC/μL, IQR 3.23–4.25 in CM group versus 4.42 106 RBC/μL, IQR 4.0–4.67 in the meningitis group). Platelet count was 67.5 109/μL (IQR 59–161) for CM and 246 109/μL (IQR 191–383) for meningitis patients, indicating a thrombocytopenia in the CM group.

3.2. Analyte differences between the CM and meningitis group:

To assess differences in vascular dysfunction, both plasma and CSF levels of Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) (Figure 1) and s-ICAM-1 (Figure 2) were tested.

Figure 1: Differences in Angiopoietin values in plasma and CSF of children with CM or meningitis.

Figure 1:

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Both Angiopoietin 1 and angiopoietin 2 levels in plasma and CSF of meningitis patients are higher than those in CM patients. Log10 values are indicated on Y-axis. The ratio of plasma Ang1:Ang2 in CM patients is higher than that is meningitis patients, whereas there is no significant difference in the CSF.

Figure 2: Marker of vascular inflammation marker s-ICAM-1.

Figure 2:

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Values of the vascular inflammation marker s-ICAM-1 is not significantly different in plasma and CSF of both patient groups, although there is a greater variation in CSF of meningitis patients. Log10 values are indicated on Y-axis.

Overall, the plasma values for both Angiopoietins were higher than the CSF levels. Despite the fact that the plasma Ang-2 levels were not different between the two groups, the Ang-1 concentrations in plasma were higher in the meningitis group (p=0.008). This resulted in a significantly higher plasma Ang-2:Ang-1 ratio in the CM, as compared with the meningitis group (p=0.024). However, the plasma ratio of Ang-2:Ang-1, was found to be higher in the CM than the meningitis group. Previously, a higher plasma Ang-2:Ang-1 ratio was reported for CM patients compared to patients with severe malaria 9, 10, 13. This ratio is also a predictive of the outcome in sepsis patients, with a higher plasma ratio (median 15.6) associated with death, whereas lower ratios (median 3) were associated with survival 14. The increases in these specific markers for vascular inflammation clearly indicate a general vascular dysfunction in both CM and meningitis.

As for CSF Ang-1, this was in general low, with a few patients showing a slightly higher Ang-1 level. CSF-Ang-2 levels were relatively high in both groups, which is similar to a report on children with bacterial meningitis 15. In CM, elevated CSF-Ang-2 was shown to be related to BBB dysfunction 16 and elevated neuronal expression correlates with ring hemorrhages 17, also suggesting blood-brain barrier damage. Moreover, elevated CSF levels of Ang-2 are correlated to worse outcomes in different cognitive domains (gross motor, visual reception and language) in children below 5 years but not older children 18.

In this study, both groups show a similar increase in CSF Ang-2 levels, suggesting that BBB dysfunction similarly occurs in both CM and meningitis patients and that both patients groups are at increased risk for cognitive dysfunction. No differences were found in the CSF Ang2:Ang-1 ratio between these two diagnostic groups.

To assess endothelial inflammation, we tested s-ICAM-1 levels (Figure 2). Plasma levels of s-ICAM-1 are low in healthy individuals but on an inflamed endothelium ICAM-1 is overexpressed and plays a role in immune cell transmigration. As expected, the levels of s-ICAM-1in plasma were higher in both groups, as compared with CSF, but with no significant differences between the groups. In CM, an elevated ICAM-1 expression on brain endothelium can increase PRBC sequestration, as suggested by in vitro data19. The increased presence of proteases in inflammation, including CM, leads to cleavage of ICAM-1 resulting in an elevation of s-ICAM levels. Increased s-ICAM-1 levels in plasma of the CM patients 20–22 and those with other infections is in agreement with previously reported data (see review Page & Liles23). Levels of s-ICAM-1 were lower in CSF, but overall, a higher median and larger spread was found for CSF levels of s-ICAM-1 in the meningitis group.

The reason for this difference is unclear but ICAM-1 expressed on astrocytes and microglial cells may be cleaved off by metalloproteases24 and, as such, contribute to the increased s-ICAM in the CSF. As seen in both human CM 25 and experimental murine eCM 26–28, rat sepsis models 29, 30 and viral encephalitis 31, ICAM-1 expression is often associated with immunoreactive glial fibrillary acidic protein (GFAP)-positive astrocytes and thus indicative of increased brain inflammation. The higher s-ICAM levels in CSF in the meningitis group are likely due to an invasion of either virus or bacteria and/or their products into the CNS neuropil, causing increased astroglial inflammation, compared to CM where PRBC do not cross the BBB into the CNS. Increases in CSF s-ICAM-1 levels are linked to diverse neuro-pathologies, including the risk for developing a posttraumatic depressive syndrome 32. Similar to humans, septic rats present recognition memory impairment 30. Thus, potentially, increases of s-ICAM-1 in the CSF of CM patients could be a marker for post CM sequelae.

As the s-ICAM-1 levels in plasma were found to be similar in both groups, comparable vascular activation was implicated. However, the increased plasma ratio of Ang-2:Ang-1 suggests an overall higher vascular inflammation in CM, likely caused by the sequestered PRBC’s.

Peripheral inflammation, as indicated by levels of IL-6 and IL-8 in plasma, was similar in both groups (Figure 3). Similarly, in the CSF, no significant differences were observed for IL-8. Notably, the concentrations of IL-8 in the CSF were higher than in the plasma of both groups, indicative of a high level of CNS inflammation. Surprisingly, although plasma levels of IL-6 did not differ significantly between the CM and meningitis group (p=0.228), the IL-6 levels in CSF were significantly higher in the meningitis group (p<0.001). In this case, the CSF/plasma ratio was also elevated. The increased intrathecal production of IL-6 and increased s-ICAM-1 suggests high astroglial inflammation in the meningitis group due to both microbial presence and increased immune influx into the brain’s neuropil, as opposed to the intravascular presence of PBRC in CM, likely with limited immune cell influx.

Figure 3: Differences in cytokine levels in plasma versus CSF in children with CM and meningitis.

Figure 3:

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Left panel: IL6 levels in plasma of CM patients is not significantly different than that in meningitis patients, however, in CSF of meningitis patients IL6 levels are significantly higher. Log10 values are indicated on Y-axis.

Right panel: IL8 values in plasma and CSF of children with CM or meningitis. IL8 in plasma of CM patients is similar to that in meningitis patients and not significantly different for both plasma and CSF. Log10 values are indicated on Y-axis.

The difference in the levels of IL-6 and IL-8 in the CSF between the two patient groups suggests that differential neuronal signaling processes are involved. In CM, the intravascular PRBC cause endothelial inflammation, whereas in the meningitis group, viral or bacterial products contribute to this. Due to an already compromised BBB, these microbial products easily enter into the CNS, leading to an increase in brain cytokines and chemokines, activation of the complement cascade, and increased immune cell-derived toxic mediators 33.

The increased plasma and CSF-IL-6 is in agreement with other reports on bacterial and viral-induced encephalopathies 34. However, besides the detrimental effects of CNS inflammation, IL6 also plays a neuroprotective role, as activated microglia express not only cytokines but also neuroprotective factors 35. Interestingly, in encephalopathies, the increased IL-6 is accompanied by increased BDNF levels. In this study, BDNF concentrations were overall much higher in plasma than in the CSF (Figure 4). In plasma, the BDNF levels were about a log higher in the meningitis group (p=0.004), as compared to the CM-group, but they were not different in the CSF. BDNF, a small 13.5 kDa protein, is in the healthy CMS synthesized by cerebral endothelial cells and neurons CNS 36. BDNF levels are normally very low and in neuroinflammation, including in meningitis and encephalitis patients, BDNF production shifts to activated astroglia37, and infiltrated immune cells are also a major source of BDNF 38,34, 39, 40 BDNF plays an important role in the developing fetal/postnatal brain, promoting growth and the development of immature neurons, synaptic plasticity, the regeneration of neurons after injury, stimulation of oligodendrocyte proliferation, and positively influences remyelination after injury 41, 42, These neuronal repair processes are important in a regenerating brain after microbial-induced neuronal damage as also seen in encephalopathies, including CM.

Figure 4: Differences in BDNF levels in plasma but not in CSF.

Figure 4:

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BDNF in plasma of CM patients is lower than that in meningitis patients, however, no statistical differences are seen in the CSF values for both groups. Log10 values are indicated on Y-axis.

The reason for the increased plasma BDNF in the meningitis patients is not clear. Possibly, this is due to differences in production/release or in clearance by the kidneys into the urine 43. Release from platelets may also contribute to the increased BDNF in plasma 44. However, CM patients had significantly lower platelet counts and only a correlation of BDNF with platelets was found with meningitis (Rho=0.5077, p=0.0011), but not with CM.

Neurotrophic factors also increase vascular permeability, suggesting a greater BBB dysfunction in the meningitis patients than in the CM patients. In addition to brain endothelial synthesis, plasma-derived BDNF can also cross the BBB through selective transporters into the CNS and as such contribute to neuronal repair 45. Morichi et al. 34 showed that there are differences in BNDF levels in viral encephalopathies with e.g. influenza having a higher BDNF level, than human herpes virus-6, respiratory syncytial virus and rotavirus but patients with bacterial meningitis displayed the highest CSF-BDNF levels. This group34 also reported that in the bacterial meningitis cases and influenza-associated encephalopathy, pediatric patients with both increased CSF-IL-6 and CSF-BDNF ended up with more neurologic sequela (r=0.69) than those with lower levels but this was not observed for the plasma-BDNF (r=0.13). Therefore, monitoring both BDNF and IL-6 levels in plasma and CSF in pediatric patients may aid in the differential prognostic diagnosis of acute CNS infections (e.g., bacterial/viral/CM meningitis/encephalopathies) and potentially predict neurologic outcome. Although in this initial study neurologic sequela were not assessed it is planned for future studies.

Correlation of analytes with blood and clinical values was tested using Spearman’s correlation coefficient. For plasma, only the platelet counts positively correlated with Angiopoietin 1 levels (Rho 0.9524, p=0.001) in CM and negatively with the Angiopoietin ratio in CM (Rho −0.9524, p=0.011) and meningitis (Rho −0.6227, p=0.097). Platelets correlated positively with BDNF in meningitis (Rho 0.5077, p=0.0393), which is in agreement with Morichi et al. 34 but in our study no correlation was found in CM. Red blood cell counts positively correlated in meningitis with Angiopoietin 1 (Rho 0.6484, p=0.0144) but negatively with the Angiopoietin ratio (−0.6967, p=0.0072). No other correlations were found in this study, e.g. with coma score or parasitemia in CM. As the parasite life cycle includes a sequestration stage, it is possible that, at admission, more parasites were sequestered than in circulation, thus not showing a correlation with the blood smears. The absence of a correlation with the coma score may be due to the small sample size. Future larger studies may shed more light on these correlations.

4: CONCLUSIONS

These results show overall higher levels of neuroinflammation, with clear increases in biomarkers of vascular inflammation and BBB damage in both the CM and meningitis patients. There are distinctly high levels of IL-6 in CSF and BDNF in the plasma of meningitis patients, compared to CM patients. This suggests that different regulatory signaling mechanisms are involved in their neuropathogenesis. A combination of IL6 and BDNF could potentially be used as an additional biomarker to discriminate between CM versus meningitis. Their respective roles in neuroinflammation and the development of neurologic sequelae deserve more attention. In addition, BDNF may represent a potential target for adjunctive therapeutic intervention for neuroprotection and to ameliorate neurologic and cognitive sequelae.

Table 1: Demographic and clinical data.

A) Shows patient’s demographic data and blood values are listed in this table with the p values.

B) Lists clinical symptoms and past history of the two patient groups with p values.

Variable Cerebral Malaria Meningitis Total P value
Age (years) 4.00 (3.11–4.9) 2.50 (2.00–9.00) 4.00 (2.31–6.10) 0.689
Weight (Kg) 16.00 (13.00–20.00) 12.00 (8.60–26.50) 14.00 (10.80–25.10) 0.384
Temperature (°C) 38.10 (36.90–39.20) 38.90 (37.80–39.20) 38.80 (37.70–39.20) 0.322
BCS (score) 8.00 (8.00–9.00) 10.00 (9.00–15.00) 9.00 (8.00–12.00) 0.015
Hemoglobin (g/dL) 8.50 (8.40–9.60) 10.90 (9.20–11.40) 10.20 (8.40–11.40) 0.083
Hematocrit (%) 27.00 (25.10–30.00) 32.70 (29.30–35.50) 31.10 (25.90–35.50) 0.053
RBC (106/μL) 3.51 (3.23–4.25) 4.42 (4.05–4.67) 4.16 (3.50–4.60) 0.034
MCV (fL/cell) 76.25 (74.10–78.60) 76.30 (72.40–83.60) 76.30 (72.40–83.60) 0.802
MHC (pg/cell) 25.00 (24.60–26.60) 26.10 (23.00–26.70) 25.20 (23.30–26.70) 0.802
MCHC (g/dL) 33.05 (32.00–33.90) 32.90 (31.60–34.10) 32.90 (31.60–33.90) 0.919
Platelets (109/L) 67.50 (59.00–161.00) 246.00 (193.00–383.00) 221.00 (70.00348.00) 0.009
PDW (%) 13.90 (10.90–15.85) 12.45 (11.90–13.65) 12.65 (11.30–14.05) 0.426
WBC (109/L) 9.37 (8.80–12.42) 10.97 (10.63–17.41) 10.96 (8.80–13.82) 0.292
Neutrophils (109/L) 5.96 (4.23–7.31) 6.45 (4.52–10.09) 6.04 (4.32–8.26) 0.457
Lymphocytes (109/L) 2.32 (1.84–2.82) 1.67 (1.20–2.67) 2.17 (1.43–2.67) 0.244
Monocytes (109/L) 0.87 (0.76–1.14) 0.69 (0.54–1.34) 0.86 (0.62–1.14) 0.978
Eosinophils (109/L) 0.21 (0.02–0.41) 0.22 (0.02–0.39) 0.22 (0.02–0.41) >0.99 9
Basophils (109/L) 0.07 (0.03–0.16) 0.01 (0.01–0.05) 0.04 (0.01–0.06) 0.035
Protein (g/L) 65.00 (61.00–68.20) 78.10 (71.60–81.30) 70.80 (65.00–79.10) <0.001
Albumin (g/L) 40.80 (35.40–43.70) 41.60 (33.50–45.80) 41.40 (35.40–45.10) 0.452
ALT (U/L) 39.00 (23.00–46.70) 23.80 (11.00–32.20) 25.40 (18.90–39.20) 0.076
AST (U/L) 72.70 (57.10–142.80) 60.40 (34.10–72.10) 64.25 (36.70–92.30) 0.192
Sodium (mEq/L) 134.00 (132.00–136.00) 132.00 (128.50–135.00) 133.00 (130.00135.00) 0.330
Chloride (mEq/L) 100.00 (99.00–101.00) 98.20 (96.15–100.95) 99.10 (96.60101.00) 0.229
Potassium (mEq/L) 4.50 (4.20–5.44) 4.14 (3.58–5.55) 4.20 (3.71–5.44) 0.139
Urea (mg/dL) 5.04 (4.88–8.91) 3.52 (2.76–5.12) 4.59 (3.14–6.44) 0.022
Creatinine (μmol/L) 34.80 (24.50–48.00) 38.90 (31.70–48.90) 38.90 (26.10–48.00) 0.506
CSF Glucose (mg/dL) 90.00 (82.62–93.60) 77.49 (71.28–90.36) 88.02 (74.16–91.08) 0.027
CSF Chloride (mEq/L) 123.00 (120.00–126.00) 120.00 (118.00–122.00) 121.00 (119.00125.00) 0.088
Variable Malaria Meningitis Total p value
Female (%) 6 (54.55%) 6 (35.29%) 12 (42.86%) 0.444
Symptoms
Fever (>7 days) (%) 1 (9.09%) 2 (11.76%) 3 (10.71%) >0.999
Headache(%) 7 (63.64%) 11 (64.70%) 18 (64.29%) >0.999
Vomit (%) 7 (63.64%) 6 (35.29%) 13 (46.43%) 0.347
Diarrhea (%) 4 (36.36%) 7 (41.17%) 11 (39.29%) 0.703
Cough (%) 3 (27.27%) 9 (52.94%) 12 (42.86%) 0.378
Seizures (%) 8 (72.72%) 7 (43.75%) 15 (53.57%) 0.134
Past Medical History
Epilepsy 1 (9.09%) 0 (0.00%) 1 (3.57%) 0.393
Cerebral Malaria 1 (9.09%) 0 (0.00%) 1 (3.57%) 0.393
Anemia 3 (27.27%) 2 (11.76%) 5 (17.86%) 0.353
Transfusions 0 (0.00%) 1 (5.88%) 1 (3.57%) >0.999
Presenting Signs
Pallor 7 (63.64%) 2 (11.76%) 9 (32.14%) 0.010
Pyrexia 10 (90.91%) 16 (94.12%) 26 (92.86%) >0.999
Jaundice 3 (27.27%) 1 (5.88%) 4 (14.29%) 0.269
Respiratory Distress 1 (9.09%) 1 (5.88%) 2 (7.14%) >0.999
Hemoglobinuria 1 (9.09%) 1 (5.88%) 2 (7.14%) >0.999
Laboratory Results
CSF WBC (cells/field) 1 (9.09%) 9 (52.94%) 10 (35.71%) 0.041
CSF RBC (cells/field) 1 (9.09%) 7 (41.18%) 8 (28.57%) 0.099
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Highlights.

Elevated BDNF in plasma of cerebral malaria and meningitis patients

Elevated Interleukin-6 in cerebrospinal fluid of cerebral malaria and meningitis patients

Higher plasma-BDNF and CSF-interleukin-6 in meningitis patients than in those with cerebral malaria

Acknowledgements of financial support and sponsorship:

This work was supported with grant support from the NIH R21 #-TW009741, Bloomberg Philanthropies and the Malaria Research Institute to MFS.

5. List of abbreviations:

Ang

Angiopoietin

BBB

blood brain barrier

BDNF

brain derived neurotrophic factor

BCS

Blantyre coma scale

CM

cerebral malaria

CSF

cerebro-spinal fluid

s-ICAM

soluble intercellular adhesion molecule 1

IL

interleukin

IQR

interquartile ranges

KDa

kilo Dalton

L

Lumbar

RBC

red blood cells

PRBC

Plasmodium infected red blood cells

Footnotes

7.

Declarations of interest: none

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