Optimizing functional outcome endpoints for stroke recovery studies

Abstract

Novel therapeutic intervention that aims to enhance the endogenous recovery potential of the brain during the subacute phase of stroke has produced promising results. The paradigm shift in treatment approaches presents new challenges to preclinical and clinical researchers alike, especially in the functional endpoints domain. Shortcomings of the “neuroprotection” era of stroke research are yet to be fully addressed. Proportional recovery observed in clinics, and potentially in animal models, requires a thorough reevaluation of the methods used to assess recovery. To this end, this review aims to give a detailed evaluation of functional outcome measures used in clinics and preclinical studies. Impairments observed in clinics and animal models will be discussed from a functional testing perspective. Approaches needed to bridge the gap between clinical and preclinical research, along with potential means to measure the moving target recovery, will be discussed. Concepts such as true recovery of function and compensation and methods that are suitable for distinguishing the two are examined. Often-neglected outcomes of stroke, such as emotional disturbances, are discussed to draw attention to the need for further research in this area.

TMEM16F Aggravates Neuronal Loss by Mediating Microglial Phagocytosis of Neurons in a Rat Experimental Cerebral Ischemia and Reperfusion Model

“…Two hours post-occlusion, the filament was slowly withdrawn under anesthesia and animals were then returned to their cages for reperfusion (MCAO/R) ( 18 , 19 ). Animals were assessed for functional impairment using the modified Bederson grading system to verify accurate occlusion of the middle cerebral artery when the rats were awakened ( 20 , 21 ). Motor deficits were graded from 0 to 4.…”

CD36 deficiency reduces chronic BBB dysfunction and scar formation and improves activity, hedonic and memory deficits in ischemic stroke

“…Procedures on behavior tests were adopted from previous publications with minor modifications. 2,27,28…”

“…The modification of post-stroke immune responses, neovascularization, scar formation and tissue milieu to ensure an environment that will enhance endogenous recovery processes represents a novel therapeutic approach. 1,2…”

Biphasic roles of pentraxin 3 in cerebrovascular function after white matter stroke

“…Third, our experimental system of in vivo angiogenesis assays did not identify whether the newly generated endothelial cells by PTX3 downregulation were truly “functional/effective” or not. For the purpose of drug development, whether newly generated endothelial cells (and vessels) by PTX3 siRNA contributes to the recovery of cerebral blood flow and neurological function will need to be carefully assessed in future studies 45‐48 . In addition, although our study focuses only on angiogenetic responses to examine the roles of PTX3 in compensatory mechanisms after white matter stroke, brain recovery requires the coordinated responses of many different processes, including angiogenesis and neurogenesis 49,50 .…”