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

众所周知，出生后早期的经历会导致大鼠大脑和行为组织发生持久的变化，但这种变化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、产前应激和药物滥用的负面影响上。我之前的研究着眼于出生前和出生后环境刺激的潜在效用，以改善大鼠早期皮质损伤后的行为恢复。我已经证明了母体触觉刺激或复杂的住房对后来的损伤具有预防作用。我还证明了皮肤能够产生碱性成纤维细胞生长因子(bFGF或成纤维细胞生长因子-2，一种已知刺激大脑可塑性的生长因子)等蛋白质来响应触觉刺激，这些蛋白质似乎有助于从早期脑损伤中恢复。触觉刺激的幼鼠大脑皮质中成纤维细胞生长因子-2受体、成纤维细胞生长因子受体1的表达增加，而接受触觉刺激的损伤动物在剩余的额叶皮质中也表现出碱性成纤维细胞生长因子的表达上调。本研究的主要目的是了解以下几个方面：1)围产期经历(以母体或出生后触觉刺激、母体复杂住房或母体锻炼的形式)如何影响正常动物的大脑和行为发育；2)围产期体验如何与早期脑损伤相互作用，促进或抑制功能恢复；3)早期体验产生的脑发育变化如何影响后期体验对大脑可塑性的影响；4)皮肤刺激可能诱导局部产生对大脑可塑性起作用的生长因子。

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.