Abstracts

Genetic background and anesthesia duration influence hippocampal BDNF protein levels after acute TBI in rat

Abstract number : 1.044
Submission category : 1. Translational Research: 1B. Models
Year : 2017
Submission ID : 345586
Source : www.aesnet.org
Presentation date : 12/2/2017 5:02:24 PM
Published date : Nov 20, 2017, 11:02 AM

Authors :
Robert Kotloski, William S Middleton Veterans Memorial Hospital; Samantha Dunn, University of Wisconsin - Madison; and H. Alexander Chen, University of Wisconsin - Madison

Rationale: Traumatic brain injury (TBI) and its residuals including post-traumatic epilepsy are major health problems that are growing in prominence. Treatments for TBI in the acute setting include pharmacologic coma, although data supporting this treatment or its mechanism of action is limited. Genetic factors are known to influence outcome following TBI. Prior research utilizing a pair of unique and complementary in-bred rat strains selected for either increased or decreased rates of perforant path kindling has demonstrated significant differences in sequelae of TBI. The goal of this study is to examine the effects of genetic background on gene expression, protein levels of brain-derived neurotrophic factor, as well as in the influence of duration of anesthesia. Methods: Perforant path kindling susceptible (PPKS) and perforant path kindling resistant (PPKR) strains were bred from a Sprague-Dawley (SD) background, selecting for fast or slow development of perforant path kindled seizures for >15 generations. Controlled cortical impact (CCI) under isoflurane anesthesia was induced over the right temporo-parietal cortex to produce a moderate-to-severe TBI. One group of PPKS (n=5) and PPKR (n=5) rats were maintained under isoflurane anesthesia (2% in O2) for 15 minutes after the CCI, while a second group of PPKS (n=5) and PPKR (n=5) rats were treated identically, except that they were maintained under isoflurane (2%) for 60 minutes following the CCI. Rats were allowed to recover and then were euthanized at 4 hours after the end of the CCI. Control rats from the PPKS (n=2) and PPKR (n=2) strains were also included. The right hippocampus (ipsilateral to the injury) was dissected and homogenized. BDNF protein levels were determined by BDNF Emax ImmunoAssay System (Promega).Data was analyzed by a standard least squares model. Results in pg/mg total protein are presented as mean ± SEM. Results: PPKS and PPKR strains demonstrated increases in hippocampal BDNF protein levels as compared to baseline following CCI and 15 minutes of isoflurane anesthesia (PPKS baseline 175.4±5.7, 15 min isoflurane 252±14.7; PPKR baseline 98.0±12.8, 15 min isoflurane 242.4±19.2). Interestingly, comparison of the hippocampal BDNF protein levels after 15 or 60 minutes of isoflurane across the PPKS and PPKR strains demonstrated a significant interaction, with PPKS rats demonstrating a decrease in BDNF protein with 60 minutes of isoflurane (188±20.5) as compared to 15 minutes of isoflurane (252±14.7), while PPKR rats did not demonstrate significant change with 60 minutes of isoflurane (235.7±16.0) as compared to 15 minutes of isoflurane (242.4±19.2). BDNF protein levels in the PPKS rats with 60 minutes of isoflurane were not different than PPKS controls (188±20.5 vs 175.4±5.7). Conclusions: The strain-specific differences described demonstrate that selective genetic pressures to increase or decrease the rate of perforant path kindling also influence hippocampal BDNF protein levels in response to acute TBI, specifically a significant interaction of strain and duration of isoflurane anesthesia duration. While pharmacologic coma is used in the setting of acute severe TBI, data is limited as to its effectiveness, impact on long-term sequelae, and mechanism of action. The findings presented demonstrate a potential mechanism of action, dependent on genetic background. As BDNF is known to have important roles in epileptogenesis, these differences may presage differences in sequelae of TBI such as post-traumatic epilepsy. Funding: VA CDA-2 (IK2BX002986)
Translational Research