Table 1.

Molecular Effects of Therapeutic Hypothermia on HIBI and TBI

Injury Types	Protective Mechanism	Hypothermia (°C)	Hypothermia Length (Hour) /Condition	Molecular Effect	Model	Refs.
HIBI	Anti-apoptotic	34.9	12 post-ischemic	Reduce apoptotic cell death	Piglets	[44]
HIBI	Anti-apoptotic	30	72 post-ischemic	Suppress cytochrome c release and activation of caspase-3 and calpain	Wistar rat pups	[46]
HIBI	Anti-apoptotic	30	10 post-ischemic	Reduce levels of cytochrome c and activation of caspase-3 and −2	Wistar rat pups	[47]
HIBI	Anti-apoptotic	30	24 post-ischemic	Decrease phosphor-Akt and caspase-3 levels, total Akt levels remain unchanged	Sprague- dawley rat pups	[50]
HIBI	Anti-apoptotic	30–32	>24	Reduce caspase-8 and −9 activity, delay caspase-3 activation, inhibit cytochrome c and AIF release, and attenuate markers of oxidation	PC12 cells	[53]
TBI	Anti-apoptotic	32	72 /combination with propofol	Decrease tissue trauma	Organotypic hippocampal brain slices	[39]
TBI	Anti-apoptotic	30.8	24 post-injury	Suppress JNK activation and prevent apoptosis	Sprague- Dawley rats	[63]
TBI	Anti-apoptotic	32 ± 0.5	2	Decrease calpain activity	Cultured rat neurons	[65]
TBI	Anti-apoptotic	32	24, 72	Decrease the levels of caspase-3 mRNA and immunoreactivity and attenuate TIMP-3 activation	Sprague- Dawley rats	[66]
TBI	Anti-apoptotic	30	0.75/pre-injury 1/post-injury	Attenuate MAP-2 degradation	Rats	[67]
HIBI	Anti- inflammatory	33	72	Reduce levels of IL-6, IL-10, and NO	Neonatal wistar rats Microglia culture	[54]
TBI	Anti- inflammatory	30	1.5	Cold pre-conditioning evoke neuroprotection with the involvement of TNF-α, and IL-11	Rat hippocampal slices	[69]
TBI	Anti- inflammatory	35	4 post-injury	The enhancing capability of heat acclimation mice to maintain hypothermia after injury may contribute to the functional benefit of the acclimation process	Mice	[68]
TBI	Anti- inflammatory	33	3	Downregulate inflammatory response genes effects on synapse organization, Biogenesis (upregulated) and regulate the mRNA expression of Ank3, Cmbp, Nrxn3, Tgm2, and Fcgr3	Rat hippocampus	[36]
TBI	Anti- inflammatory	32–35	<24	Attenuate MMP-9 and IL-6 levels	Human patients	[70]
HIBI	Anti-oxidative	33–34	72	Decrease rise in CRP and slower rise in hydroperoxides	Term infants	[56]
TBI	Anti-oxidative	32–33	24 post-ischemia	Reduce astrocytes and inflammatory cytokine levels	Sprague dawley	[55]
HIBI	Anti-excitation	34	3	Suppress NMDA receptor phosphorylation and protein oxidation	Piglets	[57]
TBI	Anti-excitation	23, 32	0.5, 1	Attenuate the uptake of extracellular glutamate via hGLT-1	Chinese hamster ovary cells	[40]
TBI	Anti-excitation	30	24 /after 0.5–1.67 hour of oxygen glucose deprivation	Reduce the release of glutamate to the bathing medium	Murine cortical cultures	[72]
TBI	Anti-excitation	35	1–3	Attenuate excitatory damage to hippocampal neurons	Rats	[73]
HIBI	Enhance energy metabolism	33, 35	24	Prolong nucleotide triphosphate/ phosphate pool and reduce the secondary fall in phosphocreatine/inorganic phosphate ratios	Piglets	[59]
HIBI	Enhance energy metabolism	31	31 intra-ischemic	Increase high energy phosphates and glucose levels, decrease lactate levels	Rat pups	[58]
TBI	Reduce BBB disruption	30 or 33	1 /alone or combination with FK506	Reduce BBB disruption following TBI, significantly enhance vascular and axonal protection, and prevent BBB dysfunction	Rats	[76] [81]
TBI	Protect Cerebral Circulation	32	1.5	Protect cerebral microcirculation	Rats	[80]
TBI	Anti- brain edema	23.17 + 0.95 25.19 + 0.76 30.53 + 0.8 30.37 + 0.67 27.33 + 1.13 27.43 + 1.18	5 / combination with decompressive craniectomy	Reduce posttraumatic brain edema	Male CD-1 mice	[78]

Explanation of abbreviations can be found in the list of abbreviations.