Challenges of Neuroprotection and Neurorestoration in Ischemic Stroke Treatment

Abstract

Currently, the most important therapeutic approaches in the acute phase of ischemic stroke are focused on the restoration of regional cerebral blood flow, early admission to a stroke unit and the attempt to block, using neuroprotective drugs, the biochemical and metabolic changes involved in the ‘ischemic cascade’. Treatment with rt-PA in the acute phase, although very effective, is still limited to a small number of patients and positive preclinical results of neuroprotective treatment have not, as yet, been endorsed in clinical trials. The remarkable lack of concordance between the positive results in experimental models and the negative results obtained in clinical trials has led to a change in attitude in the conduct of preclinical studies as well as to a modification of the design of clinical trials, with special attention being paid to patient selection criteria and clinical evaluation. Some neuroprotective drugs, such as citicoline, have shown some efficacy in subgroups of patients with cerebral infarction, even with a therapeutic window of up to 24 h, which would suggest a possible neurorestorative effect. Different degrees of functional recovery, weeks or months after the ischemic event, are currently observed in clinical practice and have been related to endogenous self-repair mechanisms. The growing understanding of the mechanisms involved in the phenomena of brain plasticity and their modulation, together with the possibility of restoring functional deficits by encouraging endogenous neurogenesis or by cell therapy, open up new directions in the treatment of stroke patients.

Ketone bodies metabolism during ischemic and reperfusion brain injuries following bilateral occlusion of common carotid arteries in rats

“…1 At present, only recombinant tissue plasminogen activator (rt-PA) has been efficiently labeled for the management of acute stroke. 2 Understanding the role of various extrinsic and intrinsic pathogenic factors of ischemic damage represents a prime objective of ongoing stroke research. The development of experimental models of cerebral ischemia has allowed for a better knowledge of its pathophysiology and for testing new therapeutic strategies.…”

Botulinum Neurotoxin: The Ugly Duckling

“…Today, we know that the brain contains several somatic (adult) stem cells which may differentiate to functional neurons [86]. Apart from stem cells, neural circuits are established anew if intact neurons, sensing the lack of their normal neighbors, manage to send new axons to other neurons, make synapses and acquire some of the lost functions [87]. Since axon regeneration is extremely slow, a physiotherapeutic program must start immediately after the patient’s stabilization in order to inhibit muscle shortening as long as regeneration proceeds [49].…”

Neuroplasticity and Cellular Therapy in Cerebral Infarction

“…However, as mentioned above, the brain is plastic, and in some measure is able to reorganize itself in response to damage. When a neural system is completely destroyed, the brain may be able to recruit alternative systems which, under normal conditions, are not activated, but which have the capacity to ‘learn’ the lost function [18]. Thus, after a stroke, some patients recover their lost function up to a certain degree, always depending on factors such as the localization of the lesion and its size, as well as individual variations in anatomical and functional connections [19].…”