Common biochemical defects linkage between post-traumatic stress disorders, mild traumatic brain injury (TBI) and penetrating TBI

Abstract

AnxietyPsychological damage a b s t r a c t Post-traumatic stress disorder (PTSD) is a complex mental disorder with psychological and emotional components, caused by exposure to single or repeated extreme traumatic events found in war, terrorist attacks, natural or man-caused disasters, and by violent personal assaults and accidents. Mild traumatic brain injury (TBI) occurs when the brain is violently rocked back and forth within the skull following a blow to the head or neck as in contact sports, or when in close proximity to a blast pressure wave following detonation of explosives in the battlefield. Penetrating TBI occurs when an object penetrates the skull and damages the brain, and is caused by vehicle crashes, gunshot wound to the head, and exposure to solid fragments in the proximity of explosions, and other combat-related head injuries. Despite clinical studies and improved understanding of the mechanisms of cellular damage, prevention and treatment strategies for patients with PTSD and TBI remain unsatisfactory. To develop an improved plan for treating and impeding progression of PTSD and TBI, it is important to identify underlying biochemical changes that may play key role in the initiation and progression of these disorders. This review identifies three common biochemical events, namely oxidative stress, chronic inflammation and excitotoxicity that participate in the initiation and progression of these conditions. While these features are separately discussed, in many instances, they overlap. This review also addresses the goal of developing novel treatments and drug regimens, aimed at combating this triad of events common to, and underlying, injury to the brain.

Prolonged Neuropsychiatric Symptoms in a Military Service Member Exposed to Mefloquine

“…In addition to the overlap in symptoms, there exists some contrasting biochemical links between mefloquine-induced changes in the central nervous system (CNS) and the development of PTSD [23]. It has been postulated that three biochemical events (increase in markers of oxidative stress, chronic inflammation, and excitotoxicity) play roles in developing PTSD [23].…”

“…It has been postulated that three biochemical events (increase in markers of oxidative stress, chronic inflammation, and excitotoxicity) play roles in developing PTSD [23]. Mefloquine has also been shown to increase levels of oxidative stress markers in the CNS [24–26].…”

“…Connexin 36 forms the primary neuronal gap junction responsible for intercellular communication, including glutamate transmission [27]. Studies have shown that excessive glutamate release and receptor overactivation can lead to secondary neuronal death as well as PTSD [23, 28]. Pharmacologic blockade of connexin 36 can inhibit this over-activation and subsequent neuronal death [29].…”

High Baseline Postconcussion Symptom Scores and Concussion Outcomes in Athletes

“…In a related finding, the emotionaldistress response may exacerbate the pathophysiologic nature of the injury through several posited mechanisms, including oxidative stress, chronic inflammation, and excitotoxicity. 28 Alternatively, emotional stress may mediate other pathophysiologic outcomes, such as posttraumatic migraine, which is associated with worse performance on memory-composite aspects of neurocognitive testing. 29 In contrast to neurocognitive test findings, high-level symptom reporters displayed no increase in total symptom scores after SRC.…”

Targeting the nNOS/peroxynitrite/calpain system to confer neuroprotection and aid functional recovery in a mouse model of TBI

“…Other than critical care management, no currently approved therapies exist for TBI (Haddad and Arabi, 2012). Mechanistically, TBI is characterized by sustained neuronal nitroxidative stress (Cherian et al, 2004; Prasad and Bondy, 2015), due mainly to calcium-induced aberrant activity of neuronal nitric oxide synthase (nNOS). Aberrant nNOS activity results in reduced bioavailability of nitric oxide (NO) and formation of large amounts of peroxynitrite for prolonged periods.…”