Di Filippo Massimiliano, Tozzi Alessandro, Costa Cinzia, Belcastro Vincenzo, Tantucci Michela, Picconi Barbara, Calabresi Paolo
Clinica Neurologica, Università degli Studi di Perugia, Ospedale S Maria della Misericordia, Via S Andrea delle Fratte, Perugia, Italy.
Neuropharmacology. 2008 Sep;55(3):353-62. doi: 10.1016/j.neuropharm.2008.01.012. Epub 2008 Feb 13.
Stroke is the second commonest cause of death and the principal cause of adult disability in the world. In most cases ischemic injuries have been reported to induce mild to severe permanent deficits. Nevertheless, recovery is often dynamic, reflecting the ability of the injured neuronal networks to adapt. Plastic phenomena occurring in the cerebral cortex and in subcortical structures after ischemic injuries have been documented at the synaptic, cellular, and network level and several findings suggest that they may play a key role during neurorehabilitation in human stroke survivors. In particular, in vitro studies have demonstrated that oxygen and glucose deprivation (in vitro ischemia) exerts long-term effects on the efficacy of synaptic transmission via the induction of a post-ischemic long-term potentiation (i-LTP). i-LTP may deeply influence the plastic reorganization of cortical representational maps occurring after cerebral ischemia, inducing a functional connection of previously non-interacting neurons. On the other hand, there is evidence that i-LTP may exert a detrimental effect in the peri-infarct area, facilitating excitotoxic processes via the sustained, long-term enhancement of glutamate mediated neurotransmission. In the present work we will review the molecular and synaptic mechanisms underlying ischemia-induced synaptic plastic changes taking into account their potential adaptive and/or detrimental effects on the neuronal network in which they occur. Thereafter, we will consider the implications of brain plastic phenomena in the post-stroke recovery phase as well as during the rehabilitative and therapeutic intervention in human subjects.
中风是全球第二大常见死因，也是成年人残疾的主要原因。在大多数情况下，据报道缺血性损伤会导致轻度至重度的永久性缺陷。然而，恢复过程往往是动态的，反映了受损神经网络的适应能力。缺血性损伤后在大脑皮层和皮层下结构中发生的可塑性现象已在突触、细胞和网络水平得到记录，一些研究结果表明，它们可能在人类中风幸存者的神经康复过程中发挥关键作用。特别是，体外研究表明，氧和葡萄糖剥夺（体外缺血）通过诱导缺血后长期增强（i-LTP）对突触传递的效能产生长期影响。i-LTP可能会深刻影响脑缺血后发生的皮质表征图的可塑性重组，诱导先前不相互作用的神经元形成功能连接。另一方面，有证据表明i-LTP可能在梗死周围区域产生有害影响，通过持续、长期增强谷氨酸介导的神经传递促进兴奋性毒性过程。在本研究中，我们将回顾缺血诱导的突触可塑性变化的分子和突触机制，并考虑它们对发生这些变化的神经网络的潜在适应性和/或有害影响。此后，我们将探讨脑可塑性现象在中风后恢复阶段以及人类康复和治疗干预过程中的意义。
