Functional (neurologic) recovery following transient focal cerebral ischemia in the rat requires at least 80% of ipsilateral cortical and subcortical integrity.
Though many drugs have been proven to reduce ischemia-induced brain damage in animal models, most of them have failed to reach clinical trials or, if not, have not been proven to be efficient in humans suffering stroke. Here, by performing a global analysis of recently published data in eighty nine rats subjected to middle cerebral artery occlusion (MCAO)-induced transient focal cerebral ischemia, we show that the ability of the animals to recover motor function is dependent on and highly correlated to their percentage of healthy cortex (r=0.973; P<0.001) and healthy subcortical brain structures (r=0.916; P<0.001). In addition, data analysis further reveals that neuroprotection requires preserving at least 80% and 90% of the integrity of the ipsilateral hemispheris subjected to MCAO to provide partial and full functional neurologic recovery, respectively. We suggest that this should be taken into account in preclinical pharmacological studies to estimate the actual potentially clinical interest of drugs developed for neuroprotection as well as to avoid developing further research on drugs that only provide mild to moderate histologic outcome.
Haelewyn
Benoit
B
NNOXe Pharmaceuticals, 3107 Avenue des Hôtels, Suite 18C, Québec, QC, G1W 4W5, Canada.
Rouillon
Christophe
C
Risso
Jean-Jacques
JJ
Abraini
Jacques H
JH
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology; D002544:Cerebral Infarction / Q000473:pathology* / Q000503:physiopathology; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004185:Disability Evaluation; D018450:Disease Progression; D007839:Functional Laterality; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D009609:Nitrous Oxide / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D015427:Reperfusion Injury / Q000473:pathology* / Q000503:physiopathology; D012720:Severity of Illness Index; D014978:Xenon / Q000494:pharmacology
D018696:Neuroprotective Agents; D014978:Xenon; D009609:Nitrous Oxide