ABSTRACT
Traumatic brain injury (TBI) is a major public health concern in the USA. There are approximately 2.5 million brain injuries annually, 90% of which may be classified as mild since these individuals do not display clear morphological abnormalities following injury on imaging. The majority of individuals develop neurocognitive deficits such as learning and memory impairment and recovery occurs over 3 to 6 months after mild TBI (mTBI). The hippocampus is highly susceptible to injury from mTBI due to the anatomic localization and has been implicated in the neurocognitive impairments after mTBI. Here, we investigated whether the mTBI-induced morphological and pathophysiological alterations of GABAergic interneurons in the CA1 subfield of the hippocampus recovers after 30 days in the controlled cortical impact (CCI) model of TBI. Design-based stereology shows a significant reduction in the number of GABAergic interneurons 7 days after CCI. However, the number of GABAergic interneurons is not significantly reduced at 30 days after CCI. The total number of neurons is not altered over the course of 30 days. GABAergic inhibitory currents in the CA1 subfield also show that, although there is a significant reduction in the CCI group at 7 days, the currents are not significantly different from sham controls at 30 days. We suggest that the recovery of GABAergic function in the CA1 subfield of the hippocampus observed 30 days after CCI is one of the mechanisms associated with the recovery of memory after mTBI.
Subject(s)
Brain Injuries, Traumatic/physiopathology , CA1 Region, Hippocampal/physiopathology , Hippocampus/physiopathology , Inhibitory Postsynaptic Potentials/physiology , Animals , Brain Injuries/complications , Brain Injuries/physiopathology , Brain Injuries, Traumatic/complications , Disease Models, Animal , GABAergic Neurons , Interneurons/metabolism , Male , Memory/physiology , Memory Disorders/complications , Rats, Sprague-DawleyABSTRACT
Approximately, 1.7 million Americans suffer a TBI annually and TBI is a major cause of death and disability. The majority of the TBI cases are of the mild type and while most patients recover completely from mild TBI (mTBI) about 10% result in persistent symptoms and some result in lifelong disability. Anxiety disorders are the second most common diagnosis post-TBI. Of note, TBI-induced anxiety disorders are difficult to treat and remain a chronic condition suggesting that new therapies are needed. Previous work from our laboratory demonstrated that a mild TBI induced an anxiety-like phenotype, a key feature of the human condition, associated with loss of GABAergic interneurons and hyperexcitability in the basolateral amygdala (BLA) in rodents 7 and 30 days after a controlled cortical impact (CCI) injury. We now confirm that animals display significantly increased anxiety-like behavior 30 days after CCI. The anxiety-like behavior was associated with a significant loss of GABAergic interneurons and significant reductions in the frequency and amplitude of spontaneous and miniature GABAA-receptor-mediated inhibitory postsynaptic currents (IPSCs) in the BLA. Significantly, subchronic treatment with alpha-linolenic acid (ALA) after CCI prevents the development of anxiety-like behavior, the loss of GABAergic interneurons, hyperexcitability in the BLA and reduces the impact injury. Taken together, administration of ALA after CCI is a potent therapy against the neuropathology and pathophysiological effects of mTBI in the BLA.
