Fusion or Fission: The Destiny of Mitochondria In Traumatic Brain Injury of Different Severities

Abstract

Mitochondrial dynamics are regulated by a complex system of proteins representing the mitochondrial quality control (MQC). MQC balances antagonistic forces of fusion and fission determining mitochondrial and cell fates. In several neurological disorders, dysfunctional mitochondria show significant changes in gene and protein expression of the MQC and contribute to the pathophysiological mechanisms of cell damage. In this study, we evaluated the main gene and protein expression involved in the MQC in rats receiving traumatic brain injury (TBI) of different severities. At 6, 24, 48 and 120 hours after mild TBI (mTBI) or severe TBI (sTBI), gene and protein expressions of fusion and fission were measured in brain tissue homogenates. Compared to intact brain controls, results showed that genes and proteins inducing fusion or fission were upregulated and downregulated, respectively, in mTBI, but downregulated and upregulated, respectively, in sTBI. In particular, OPA1, regulating inner membrane dynamics, cristae remodelling, oxidative phosphorylation, was post-translationally cleaved generating differential amounts of long and short OPA1 in mTBI and sTBI. Corroborated by data referring to citrate synthase, these results confirm the transitory (mTBI) or permanent (sTBI) mitochondrial dysfunction, enhancing MQC importance to maintain cell functions and indicating in OPA1 an attractive potential therapeutic target for TBI.

Antioxidant Therapies in Traumatic Brain Injury

“…The concussed brain is characterized by transient alteration of ionic homeostasis, imbalanced cellular calcium exchange and storage, which leads to mitochondrial dysfunction with an energy crisis. Glucose dysmetabolism [120], alteration of the mitochondrial quality control [121,122], impairment of cell energy state [121][122][123], and increase of ROS and RNS production [124] characterize a temporal window following concussion during which the brain is "metabolically vulnerable" It has been clearly demonstrated that alterations of brain metabolism last much longer than symptom disappearance and return of neurocognitive functions to pre-impact levels. A second concussive event of even lesser magnitude than the first, falling within this period of vulnerability, may have catastrophic consequences causing a clinical condition termed as second impact syndrome (SIS).…”

Non-toxic engineered carbon nanodiamond concentrations induce oxidative/nitrosative stress, imbalance of energy metabolism, and mitochondrial dysfunction in microglial and alveolar basal epithelial cells

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