The Recovery of GABAergic Function in the Hippocampus CA1 Region After mTBI
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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.
KeywordsTraumatic brain injury Hippocampus GABAergic interneurons Hyperexcitability NMDA receptors memory impairment Recovery
This research was sponsored by the United States Army Research Office and the Defense Advanced Research Projects Agency (DARPA) and was accomplished under the Cooperative Agreement Number: W911NF-14-2-0100.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
All experiments using animals were conducted following the Guide for the Care and Use of Laboratory Animals (Institute of Laboratory Animal Resources, National Research Council) and were in accordance with the guidelines and approved by the Uniformed Services University of the Health Sciences Institutional Animal Care and Use Committees (IACUC). All efforts were made to minimize the number of animals used and any pain or distress associated with these experiments.
The views and conclusions contained within this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the Army Research Office, DARPA, or the United States Government.
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