Perinatal experience alters brain development and functional recovery after cerebral injury in rats

众所周知，早期的产后经历会引起大鼠大脑和行为组织的持久变化，但其发生的细节仍然知之甚少。此外，针对母亲经历在胎儿大脑发育中的作用的研究主要集中在营养不足、产前压力和药物滥用的负面影响上。我之前的研究着眼于产前和产后环境刺激对大鼠早期皮质损伤后行为恢复的潜在效用。我已经证明，母亲的触觉刺激或复杂的住房对后来的伤害有预防作用。我还证明，皮肤能够产生蛋白质，如碱性成纤维细胞生长因子（bFGF或FGF-2，一种已知能刺激大脑可塑性的生长因子），以应对触觉刺激，这些蛋白质似乎有助于早期脑损伤的恢复。触觉刺激的幼鼠皮层中FGF-2和fgfr1受体的表达增加，而接受触觉刺激的病变动物的剩余额叶皮层中bFGF的表达也上调。本研究的主要目的是了解：1)围产期经验（母体或产后触觉刺激、母体复杂住房或母体运动的形式）如何影响正常动物的大脑和行为发育；2)围产期经历如何与早期脑损伤相互作用促进或抑制功能恢复；3)早期经验对大脑发育的影响如何影响后期经验对大脑可塑性的影响；4)皮肤刺激诱导局部生长因子产生的可能性，这些生长因子在大脑可塑性中起作用。

It has been well established that early postnatal experience causes lasting changes in cerebral and behavioral organization in the rat but the details of how this happens are still poorly understood. In addition, studies directed at the role of maternal experience in fetal brain development have focused mainly on the negative effects of inadequate  nutrition, prenatal stress, and drug abuse.  My previous research looked at the potential utility of pre- and postnatal environmental stimulation to improve behavioral recovery after early cortical injury in rats. I have shown maternal tactile stimulation or complex housing has a prophylactic effect on later injury.  I have also demonstrated that the skin is capable of producing proteins like basic fibroblast growth factor (bFGF or FGF-2, a growth factor known to stimulate plasticity in brain) in response to tactile stimulation and these proteins appear to facilitate recovery from early-brain injury. Tactilely stimulated pups showed increased expression of the receptor for FGF-2, FGFR1in the cortex and lesion animals that received tactile stimulation also showed an upregulation of bFGF expression in the remaining frontal cortex.  The main goals of the proposed research are to gain an understanding of the following: 1) How perinatal experience (in the form of maternal or postnatal tactile stimulation, maternal complex housing, or maternal exercise) affects brain and behavioral development in normal animals; 2) How perinatal experience interacts with early brain injury to promote or inhibit functional recovery; 3) How changes in brain development produced by early experience influence the impact of later experience on brain plasticity; 4) The potential for skin stimulation to induce local production of growth factors that play a role in brain plasticity.