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

From: A systematic review of neuroprotective strategies after cardiac arrest: from bench to bedside (part II-comprehensive protection)

Therapy Proposed mechanism Study subject Blind Placebo control Random assignment Delivery route Effect: Outcomes evaluated
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 [3032] Promote neuronal survival and neurogenesis [29] Mice Not mentioned [30, 31] Yes Yes Intravenous [30, 31] Positive Neurological function [31] Neurohistopathology [3032]
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 [4144] Increase level of antioxidant glutathione and/or scavenging oxygen species, anti apoptosis and anti-inflammation [3739] Mice [4143] Not mentioned [41, 42, 44] Yes Not mentioned Intravenous Positive when delivered at or prior to CPR initiation [4143] Survival, neurologic function, neurohistopathology [4144]
Open KATP chanel [3537] 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]