Differential acute gene expression changes after 5 types of traumatic injury in spinal cord and the brain

Poster (konferens), 2010

Although a general poor outcome of lesions in mammalian central nervous system there are some interesting regional differences in the response to traumatic injury. There are indications that the inflammatory pattern and the duration of traumatic defects in the Blood Brain Barrier are dissimilar in the brain and the spinal cord. In this study we have examined the acute gene expression response in the adult rat after two types of traumatic brain injury (TBI) and two types of lesions affecting the spinal cord. The TBI models were an exposure to blast overpressure (200 kPa), a sagittal acceleration injury and a cortical penetration injury. The spinal injuries were lumbar ventral root avulsion at the border between the CNS and PNS. Ventral root avulsion is not followed by spontaneous regrowth. The second spinal injury was replantation of avulsed spinal ventral roots, enabling significant and useful regrowth of motor axons. In this study we have analyzed the acute response to these 5 types of injury with gene arrays combined with cluster analysis of gene ontology search terms. 3 adult Sprague-Dawley rats for each of the 5 models were used. 24 h after the injury, the animals were anesthetized and the inferior vena cava was cut open. The hippocampus and the cortex were used for analysis of the 3 TBI models and the ipsilateral ventral quadrat of the affected spinal cord segment was used for the spinal injuries. RNA samples were analysed was then hybridized to Affymetrix Rat Gene ST 1.0 array. The data show significant differences between rats subjected to ventral replantation compared to avulsion only. Whereas, the number of genes related to cell death is similar in the two models after 24 hours, we observed a significantly larger number of genes related to neurite growth and development in the rats treated with ventral root replantation. In addition, an acute inflammatory response was observed after avulsion, while effects on genes related to synaptic transmission were much more pronounced after replantation than after avulsion without replantation. Blast overpressure induced limited shifts in gene expression in the hippocampus. The most interesting findings were a down regulation of genes involved in neurogenesis and synaptic transmission. Acceleration and penetration injuries resulted in changes in the expression in a large number of gene families including cell death, inflammation and neurotransmitters in the hippocampus and the cortex. We, conclude that cluster analysis of gene ontology search terms analysis may facilitate the comparison of the acute response in different types of injury.