Themes and Strategies for Studying the Biology of Stroke Recovery in the Poststroke Epoch

Abstract

Background and Purpose-This review will focus on the emerging principles of neural repair after stroke, and on the overlap between cellular mechanisms of neural repair in stroke and clinical principles of recovery and rehabilitation. Summary of Review-Stroke induces axonal sprouting and neurogenesis. Axonal sprouting occurs in tissue adjacent to the stroke and its connected cortical areas, and from sites that are contralateral to the infarct. Neurogenesis produces newly born immature neurons in peri-infarct striatum and cortex. Stimulation of both axonal sprouting and neurogenesis is associated with improved recovery in animal models of stroke. A unique cellular environment in the poststroke brain supports neural repair: an association of angiogenic and remodeling blood vessels with newly born immature neurons in a neurovasclar niche. Controversies in the field of neural repair after stroke persist, and relate to the locations of axonal sprouting in animal models of stroke and how these correlate to patterns of human remapping and recovery, and to the different models of stroke used in studies of neurogenesis. Conclusions-On a cellular level, the phenomenology of neural repair after stroke has been defined and unique regenerative environments in the poststroke brain identified. As the field moves toward specific studies of causal mechanisms in poststroke repair, it will need to maintain a perspective of the animal models suited to the study of neural repair after stroke as they relate to the patterns of recovery in humans in this disease.

Neuron-targeted Caveolin-1 Protein Enhances Signaling and Promotes Arborization of Primary Neurons

“…Therapeutic interventions, such as addition of growth factors or approaches to increase cAMP, are relatively ineffective because of the loss of key receptors and their downstream signaling molecules. Therefore, interventions that restore progrowth and prosurvival signaling within neurons have the potential not only to reduce neuronal loss and enhance endogenous brain repair but also to increase the efficacy of pharmacologic agents designed to improve functional outcome (26).In this report, we show that overexpression of neuron-targeted Cav-1 in primary neurons enhances expression of membrane/lipid rafts and neurotransmitter and neurotrophin receptors and increases progrowth signaling, cAMP production, and dendritic growth and arborization. Conversely, siRNA-mediated loss of Cav-1 decreases membrane/lipid rafts…”

“…Inhibitors-A major limitation to neuronal growth and repair in vivo is the presence of growth inhibitors, such as inflammatory cytokines (34) and myelin-associated glycoproteins, in the region surrounding the core of an injury (26). After injury (stroke or trauma), substantial activation of astrocytes and microglia occurs that is associated with the elaboration of inflammatory cytokines such as TNF␣ and IL-1␤.…”

“…Therapeutic interventions, such as addition of growth factors or approaches to increase cAMP, are relatively ineffective because of the loss of key receptors and their downstream signaling molecules. Therefore, interventions that restore progrowth and prosurvival signaling within neurons have the potential not only to reduce neuronal loss and enhance endogenous brain repair but also to increase the efficacy of pharmacologic agents designed to improve functional outcome (26).…”

Supplement Consumption among Post stroke Patients in Dr. Hasan Sadikin General Hospital Bandung

“…Recent studies show the existence of neuronal repair after stroke, such as neurogenesis, reorganization, and axonal sprouting. 4,5 Early functional recovery takes place on the first few days once the surrounding edema subsided. Later recovery tends to be slower, but progressive, especially with repetitive exercises in rehabilitation program.…”

Repair and regeneration properties of Ginkgo biloba after ischemic brain injury

“…This was further evidenced by the upregulation of netrin-1 and its receptors, DCC and UNC5B, which mediate axonal attraction and repulsion. It is known that attractive and repulsive guidance cues dictate post-stroke axonal sprouting as well as migration of neuroblasts towards the site of the injury (Carmichael, 2008). Netrin-1 overexpression promotes neuronal migration and aids cell survival (Tang et al, 2008).…”