Table 2 Summary of comprehensive neuroprotective strategies for global cerebral ischemia associated with cardiac arrest

Pharmaceutical approaches

Adenosine [8]

Blockade Ca²⁺ influx [10] Hypothermia [8]

Rats

Not mentioned

Yes

Yes

Intravenous

Positive

Survival, regional blood flow, brain edema, metabolite assay, neurohistopathology, temporalis muscle temperature

BDNF [14]

Up regulate Bcl-2, suppress TNF-alpha, increase IL-10, reduce excitotoxicity, promote neural regeneration and axonal sprouting/synaptogenesis [11]

Rats

Not mentioned

Yes

Not mentioned

Intracerebro-ventricular

Neutral

Survival, neurologic function, neurohistopathology

IGF-1/GPE [19, 21]

Anti-apoptosis, modulation of BBB permeability and neuronal excitability [17]

Rats

Not mentioned

Yes

Yes

Intravenous [19]

Positive when combined with TH [19]

Neurologic function [19]

HIF-1 alpha activation [18]

Intracerebro-ventricular [21]

Short-term: Positive; Long-term: Neutral [21]

Neurohistopathology [18, 21]

G-CSF [25, 26]

Anti-apoptosis, anti-inflammation and enhance neurogenesis [23]

Rats

Not mentioned

Yes

Yes [25]

Subcutaneous [25]

Positive [25]

Survival, neurologic function, neurohistopathology [25, 26]

Not mentioned [26]

Intracerebro-ventricular [26]

Long-term: Negative [26]

p-STAT3, p-AKT1/2/3 and p-ERK1/2 [25]

Estrogen [30–32]

Promote neuronal survival and neurogenesis [29]

Mice

Not mentioned [30, 31]

Yes

Yes

Intravenous [30, 31]

Positive

Neurological function [31] Neurohistopathology [30–32]

Increase expression of SK2 [32]

Yes [32]

Subcutaneous [31, 32]

Small-conductance calcium-activated potassium (SK2 and SK3) channel transcripts, electrophysiology [32]

Reduce excitoxicity [33, 34]

Gas-mediator approaches

H₂S [41–44]

Increase level of antioxidant glutathione and/or scavenging oxygen species, anti apoptosis and anti-inflammation [37–39]

Mice [41–43]

Not mentioned [41, 42, 44]

Yes

Not mentioned

Intravenous

Positive when delivered at or prior to CPR initiation [41–43]

Survival, neurologic function, neurohistopathology [41–44]

Open K_ATP chanel [35–37]

Pigs [44]

Yes [43]

Neutral when delivered 10 min after CPR [41]

Myocardial function, serum nitrite/nitrate levels and hydrogen peroxide level, cardiac mitochondrial swelling [41]

Enhance NMDA receptors [38]

Negative [44]

Diffusion weighted imaging and MMP-9 activity [42]

Cardiac output, heart rate and pulmonary arterial pressure [44]

HBO [52, 53]

Attenuation of oxidative and inflammatory injury, inhibition of apoptosis, enhance neurogenesis [47, 48]

Dogs [52]

Not mentioned

Yes

Yes [52]

Inhaled

Positive

Neurologic function [52] Neurohistopathology [52, 53]

Rats [53]

Not mentioned [53]

Oxygen extraction ratio and cerebral oxygen delivery/utilization [52]

Expression of Nogo-A/B, Nogo receptors and RhoA expressions [53]

H₂[57, 58]

Anti-oxidant, anti inflammation and anti-apoptosis [55, 56]

Rats [57]

Not mentioned

Yes

Yes

Inhaled [57]

Positive

Survival, neurologic function, neurohistopathology [57, 58]

Rabbit [58]

Intraperitoneal [58]

Myocardial function, cardiomyocyte degeneration, lung edema and systemic inflammatory response [57]

Plasma 8-OHDG and MDA level [58]