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

Abstract

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 (10 g, impactor head 2.5 mm diameter, weight drop 50 mm) and compared to sham surgery controls. The novel object recognition and error ladder tests were performed at 24 hours 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.

Maternal Cigarette Smoke Exposure Worsens Neurological Outcomes in Adolescent Offspring with Hypoxic-Ischemic Injury

“…This test evaluates short-term memory retention. Each mouse was placed in a dark-colored box containing two identical green square blocks for two 5-min sessions, familiarization and test phases (5 min interval) as we have published ( Chen et al, 2016 ). During the test phase, one of the objects was replaced with an orange triangular shaped object.…”

Modulation of neural regulators of energy homeostasis, and of inflammation, in the pups of mice exposed to e-cigarettes

“…In this short report, we did not attempt to carry out mechanistic studies and were unable to measure protein levels due to a lack of sample availability. Whilst this is a limitation of the current study, our previous research has concomitant increases in mRNA and protein as expected [7,8,10]. We used two types of e-cigarettes fluids that were identical apart from the presence and absence of nicotine.…”

Astrocytic IGF-1 and IGF-1R Orchestrate Mitophagy in Traumatic Brain Injury

“…IGF-1 has shown to increase the mitophagy via activating AMPK signal [11]. We have shown mitophagy is impaired in the chronic stage of TBI [12,13], and accordingly we predict that this might be due to the lower IGF-1 status after TBI, as tau phosphorylation can disrupt the mitophagy [14]. We also nd astrocytes have a supporting role for neurons and protect against excitotoxic injury with IGF-1 dependent [15,16].…”