Moderate traumatic brain injury is linked to acute behaviour deficits and long term mitochondrial alterations.

Publication Type:
Journal Article
Citation:
Clinical and experimental pharmacology & physiology, 2016
Issue Date:
2016-08-25
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Traumatic brain injury (TBI) remains one of the leading causes of death and disability worldwide. Mild TBI may lead to neuropsychiatric sequelae, including memory loss and motor impairment. Mitochondrial dysfunction and oxidative stress have a contributory role in several neurological disorders; however, their association with mitophagy in mild TBI is unclear. TBI was induced in female Sprague Dawley (SD) rats using a New York University Impactor (10g, impactor head 2.5mm diameter, weight drop 50mm) and compared to sham surgery controls. The novel object recognition and error ladder tests were performed at 24h and for 6 weeks post-injury, and the brains were examined histologically to confirm the extent of injury. Mitochondria Manganese Superoxide Dismutase (MnSOD) and the Oxidative Phosphorylation (OXPHOS) complexes I-V (CI-CV), as well as mitophagy markers, dynamin related protein 1 (DRP-1), LC3A/B and PTEN-induced putative kinase 1 (PINK-1), were measured in the penumbra by western blot. At 24 hours sham rats performed as expected on a novel object recognition test while TBI rats showed cognitive deficits at the early time points. TBI rats also showed more early motor deficits on a horizontal ladder, compared with the sham rats. MnSOD, OXPHOS CI, CIII and CV protein levels were significantly lower in the TBI group at 24 hours. DRP-1, LC3A/B I and II, and PINK-1 were increased at 6 weeks suggesting abnormal mitophagy. Moderate TBI caused immediate cognitive and mild motor functional deficits in the rats that did not persist. Reduced antioxidative capacity and possibly compromised mitochondrial function may affect the long-term functional recovery. This article is protected by copyright. All rights reserved.
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