Contralateral structure and molecular changes after severe unilateral brain injury

Abstract

Severe unilateral brain injury has a poor prognosis and results in global brain changes, especially in corresponding contralateral regions. Understanding molecular changes in the contralateral hemisphere, especially gene regulation, may aid in discovering therapies to enhance recovery. In this study, we performed right motor cortex resection to simulate severe unilateral brain injury in male rats and investigated changes in glial and synaptic immunohistology and morphology in the left motor cortex. Transcriptome analysis was performed to examine changes in gene expression. 7 days after cortical resection, the number of reactive astrocytes and microglia with hypertrophic morphology and expression of synapsin-1 in the contralateral motor cortex was higher in the experimental group. The molecular alterations were consistent with observed structural changes such as staggered dendrites and presence of synapses around astrocytes. Genome-wide transcriptomic data indicated that pathways related to inflammation, synapses, and axonal regeneration were significantly upregulated in the contralateral cortex of the cortical resection group. Furthermore, transcription factors such as NF-KB1, Rela, STAT3, and Jun, were predicted to regulate the contralateral changes. Quantitative reverse transcription polymerase chain reaction showed that the mRNA level of Cacna1c, Tgfb1, and Slc2a1 which were regulated by STAT3, JUN and NF-KB in the contralateral cortex was higher in the cortical resection group. In conclusion, the contralateral response to unilateral brain injury was related to inflammatory and synaptic activity.