演題詳細
Oral
神経炎症と炎症性神経疾患
Neuroinflammation and Inflammatory Disease in Nervous System
| 開催日 | 2014/9/13 |
|---|---|
| 時間 | 15:00 - 16:00 |
| 会場 | Room I（311+312） |
| Chairperson(s) | 吉良 潤一 / Jun-ichi Kira (九州大学大学院医学研究院 神経内科学 / Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyusyu University, Japan) 錫村 明生 / Akio Suzumura (名古屋大学環境医学研究所 神経免疫 / Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Japan) |
Biochemical, histological and proteomic characterization of contusion and pericontusion during traumatic brain injury
- O3-I-3-4
- Harish Gangadharappa:1 Anita Mahadevan:2 Nupur Pruthi:3 Vinuth NP:4 Keshava prasad TS:4 Shankar SK:2 Srinivas Bh MM:1
- 1:Neurochemistry, NIMHANS, Bangalore, India 2:Neuropathology, NIMHANS, Bangalore, India 3:Neurosurgery, NIMHANS, Bangalore, India 4:Institute of Bioinformatics, Whitefield, Bangalore, India
Traumatic brain injury (TBI) involves pathologically distinct regions of injury called Contusion (injured tissue) and pericontusion (surrounding contused tissue). These regions could be implicated in secondary injury events following injury. We sought to characterize the injured tissue to elucidate the secondary injury pathways.
Contusion (n=20) and pericontusion (n=16) tissues obtained from autopsy and from TBI patients undergoing craniotomy. Age matched pathologically normal frontal cortex tissues which were farthest from the site of injury served as controls. Assays for oxidative stress and antioxidant function; immunohistochemistry for GFAP, phosphorylated Neurofilament, ubiquitin and tau; and LC-MS based proteomics followed by bioinformatic analysis was carried out.
Study demonstrated extensive oxidative damage evidenced by altered redox markers consistent decrease of antioxidant enzymes such as SOD and GSH metabolic enzymes and ATP depletion in the contused tissues. Total GSH was significantly decreased both in the synaptosomal and mitochondrial fractions both in contusion and pericontusion. Oxidative stress markers such as lipid peroxides, and protein carbonyls were elevated in the contusion.
Histological evaluation showed significant demyelination and increased dystrophic neurons in pericontusion. Astrogliosis (GFAP) was more in contusion compared to pericontusion. Microglial activation as seen by Iba1+ cells, oedema and axotomy was more in pericontusion compared to contusion. Functional annotation of proteomics data showed down-regulation of synaptic proteins and up-regulation of inflammatory proteins in contusion. Pericontusion showed down-regulation of structural/cytoskeletal proteins and up-regulation of negative cell regulation proteins. Mitochondrial proteins were commonly down-regulated in both contusion and pericontusion compared to normal controls. We believe that the current data gives insight into the pathology related to secondary damage and subsequently helps to understand the dynamics of head injury