NEUROSCIENCE

脑缺血发生时，动脉血液供应的大脑受阻，导致脑损伤或梗死区域。由此产生的缺血性脑损伤伴随着神经元、胶质细胞和脑血管中炎症分子、细胞因子和活性氧的合成增加。缺血和诱导的细胞因子均上调下游促炎分子的表达。缺血性脑损伤的促炎反应与梗死面积增加和神经预后不良有关；因此，阻断炎症的化合物可能是治疗脑缺血的有效疗法。神经调节蛋白是一种与表皮生长因子（EGF）结构相关的多营养生长因子。神经调节蛋白转录本在神经元和脑血管中被检测到，而其受体（erbBs）主要在大脑皮层、海马、小脑和胆碱能核的神经元中表达。从我们实验室的初步数据表明，神经调节蛋白抑制细胞因子诱导的基因表达皮层和

Cerebral ischemia occurs when the arterial blood supply to the brain is obstructed, resulting in areas of brain damage or infarcts. The resulting ischemic brain injury is accompanied by the increased synthesis of inflammatory molecules, cytokines and reactive oxygen species in neurons, glia and in the cerebral vasculature. Both ischemia and the induced cytokines upregulate the expression of downstream proinflammatory molecules. The pro-inflammatory response to ischemic brain injury is associated with increased infarct size and poor neurological prognosis; therefore compounds that block inflammation are potentially useful as therapies to treat cerebral ischemia. Neuregulin is a pleitrophic growth factor structurally related to epidermal growth factor (EGF). Neuregulin transcripts have been detected in neurons and cerebral blood vessels while its receptors (erbBs) are expressed primarily in neurons in the cerebral cortex, hippocampus, cerebellum and cholinergic nuclei. Preliminary data from our laboratory demonstrate that neuregulin inhibits cytokine-induced gene expression in cultures of cortical and hippocampal neurons. Several recent reports have implicated a role for neuregulin in the protection of neurons against brain injury. Neuregulin decreased inflammation, pro-inflammatory gene expression and demyelination in a mouse model of experimental autoimmune encephalomyelitis (EAE). Neuregulin and its receptors were shown to be upregulated in experimental models of traumatic and mechanical brain injury. In each case, the induction of neuregulin and erbBs was localized to cells at the edge of the lesion (penumbra) suggesting a role for neuregulin and erbBs in neural protection and repair. A specific role for neuregulin in ischemic brain injury has not been elucidated. Therefore, we will examine the potential neuroprotective effect of neuregulin and erbB receptor induction in a rodent model of brain ischemia using the following aims: (1) Investigate the expression of neuregulin or erbB receptors ischemic brain injury using a rat middle cerebral artery occlusion (MCAO) model, (2) To examine the expression of neuregulin and its receptors by rat neuronal cells in culture following exposure to hypoxia and (3) Investigate the effects of neuregulin on baseline, hypoxia and cytokine-induced inflammatory gene in rat neuronal cultures and examine neuroprotective effects of neuregulin on cortical cells. These studies will increase our understanding of neuregulin and potentially lead to development of new therapies that will improve clinical outcomes among patients who are treated for acute stoke.