Neurorepair versus Neuroprotection in Stroke

Abstract

Stroke is the second to third leading cause of death and the main cause of severe, long-term disability in adults. However, treatment is almost reduced to fibrinolysis, a therapy useful in a low percentage of patients. Given that the immediate treatment for stroke is often unfeasible in the clinical setting, the need for new therapy strategies is imperative. After stroke, the remaining impairment in functions essential for routine activities, such as movement programming and execution, sensorimotor integration, language and other cognitive functions have a deep and life-long impact on the quality of life. An interesting point is that a slow but consistent recovery can be observed in the clinical practice over a period of weeks and months. Whereas the recovery in the first few days likely results from edema resolution and/or from reperfusion of the ischemic penumbra, a large part of the recovery afterwards is due mainly to brain plasticity, by which some regions of the brain assume the functions previously performed by the damaged areas. Neurogenesis and angiogenesis are other possible mechanisms of recovery after stroke. An understanding of the mechanisms underlying functional recovery may shed light on strategies for neurorepair, an alternative with a wide therapeutic window when compared with neuroprotective strategies.

Improving Outcome after Stroke: Overcoming the Translational Roadblock

“…‘Learning from nature’ by inducing such mechanisms or treating with the effector molecules may result in more effective treatment with fewer unwanted side effects. In addition, only recently have we learnt that the brain, albeit with incomplete success, attempts to repair itself [11, 12]. …”

Neuroprotection in Animal Models of Global Cerebral Ischemia

“…Activation of DNA fragmentation enzymes and energy-consuming DNA repair enzymes, finally lead to DNA breakdown, interruption of protein synthesis, and cell death (Iadecola & Alexander, 2001;Leker & Shohami, 2002). In addition to the above mentioned cellular processes of ischemic damage, brain ischemia/reperfusion may also trigger cellular mechanisms for neuronal repair, and functional recovery through neuronal plasticity involving remaining neurons in vulnerable damaged or undamaged brain structures (Barone & Feuerstein, 1999;Bendel et al, 2005;Crepel et al, 2003;Hurtado et al, 2006;Jourdain et al, 2002;Ruan et al, 2006). The different ischemia/reperfusion induced cellular mechanisms leading either to brain injury and neuronal death, or to neuronal repair, as well as plasticity and brain functional recovery, may occur in a sequential or simultaneous manner.…”

Neuroplasticity and Cellular Therapy in Cerebral Infarction

“…After days or weeks, neurological deficits reflect the size and location of the structural lesions more closely. Recovery of function from this time point can be explained in terms of plasticity involving anatomical and functional reorganization of the brain tissue [10, 11]. It has been demonstrated in experimental stroke models that ischaemia in the adult brain leads to molecular and cellular changes, both perilesional and in other parts of the brain, which had previously only been observed in embryonic brains.…”

“…The aim of cellular therapy is to restore brain function by replacing dead cells with new ones through transplantation or stimulation of endogenous stem or precursor cells [11]. There is growing evidence that the adult stem cell system is more flexible than previously thought [73] and may be a therapeutic option for stroke [72].…”