Translating the frontiers of brain repair to treatments: Starting not to break the rules

Abstract

The field of neural repair in stroke has identified cellular systems of reorganization and possible molecular mechanisms. Conceptual barriers now limit the generation of clinically useful agents. First, it is not clear what the causal mechanisms of neural repair are in stroke. Second, adequate delivery systems for neural repair drugs need to be determined for candidate molecules. Third, ad hoc applications of existing pharmacological agents that enhance attention, mood or arousal to stroke have failed. New approaches that specifically harness the molecular systems of learning and memory provide a new avenue for stroke repair drugs. Fourth, combinatorial treatments for neural repair need to be considered for clinical therapies. Finally, neural repair therapies have as a goal altering brain connections, cognitive maps and active neural networks. These actions may trigger a unique set of "neural repair side effects" that need to be considered in planning clinical trials.

The translational dialogue in spinal cord injury research

“…Consequently many phase I/II clinical trials did not achieve internal (expectations of investigators) and external thresholds (approval by corporate backers or regulatory agencies, including appreciation from the clinical community) to advance towards pivotal studies. [1][2][3] Of even higher concern is the plethora of failed clinical trials, specifically in stroke (4than 50 clinical trials), which have identified some fundamental concerns by pharmaceutical companies for the field of applied clinical CNS research. Several multinational pharmaceutical companies perceive faults in the rigor of the stroke translation process, as well as long and arduous clinical trial programs with insensitive or non-specific clinical endpoints (see http://www.…”

Immunopathogenetic Aspects of Ischemic Stroke

“…Активация ростовых факторов в постинсульт-ном периоде способствует формированию ми-кроокружения, благоприятствующего спраутингу нейронов, нейрогенезу, глиогенезу, ангиогенезу и образованию аксональных коллатералей [15]. Поэтому ростовые факторы и металлопротеина-зы, продуцируемые макрофагами, нейронами, астроцитами, олигодендроцитами и эндотели-альными клетками, обеспечивают процессы вос-становления и ремоделирования поврежденной нервной ткани [15,40].…”

“…Поэтому ростовые факторы и металлопротеина-зы, продуцируемые макрофагами, нейронами, астроцитами, олигодендроцитами и эндотели-альными клетками, обеспечивают процессы вос-становления и ремоделирования поврежденной нервной ткани [15,40].…”

Avaliação clínico-experimental dos efeitos da estimulação neuronal na resposta funcional, na neuroproteção e na neuroplasticidade após isquemia cerebral. Estudo da FES em pacientes portadores de sequela de AVE em modelo experimental em ratos

“…A interpretação desses resultados permanece ambígua, já que há uma grande variabilidade nas respostas neurofisiológicas e comportamentais para as técnicas de estimulação estudadas (Bütefisch, Davis et al, 2000;Stein e Hoffman, 2003;Carmichael, 2003;Bütefisch, 2004;Cramer, 2008a;Cramer e Riley, 2008;Kleim e Jones, 2008;Richards, Stewart et al, 2008;Murphy e Corbett, 2009;Benowitz e Carmichael, 2010;Carmichael, 2010;Wittenberg, 2010).…”

“…Nesse sentido, uma nova área de atuação surge como perspectiva futura promissora no entendimento dos mecanismos que regulam a recuperação funcional após o AVE: o uso terapêutico da estimulação da plasticidade do SNC (Murphy e Corbett, 2009;Benowitz e Carmichael, 2010;Carmichael, 2010;Howells e Donnan, 2010). De modo que novas terapias biológicas e de reabilitação baseadas na estimulação da neuroplasticidade tem sido estudadas.…”