A new model of repeat mTBI in adolescent rats

Ondek, Katelynn; Brevnova, Olga; Jimenez-Ornelas, Consuelo; Vergara, Audrey R.; Zwienenberg, Marike; Gurkoff, Gene G.

doi:10.1016/j.expneurol.2020.113360

Cited by 11 publications

(8 citation statements)

References 58 publications

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“…As each impact was unique, we considered each of the injuries as an individual measure and compared values between days 35 (Repeat group only), 38 (Repeat group only) and 41 (both Single and Repeat groups). There were no significant differences in impact velocity (F (3,48) = 0.7695, p = 0.5168) or depth (F (3,48) = 0.5169, p = 0.6727) across injuries based on a one-way ANOVA [1] .…”

Section: Methods Validationmentioning

confidence: 90%

“…Animals were pretreated with carprofen (5 mg/kg, s.c.; Dechra Pharmaceuticals, Northwitch, United Kingdom) 30 min prior to initiation of anesthesia. As previously described [1] , rats were anesthetized in 4% isoflurane (in air). After reaching a surgical plane of anesthesia, the animals’ heads were shaved, and they were placed on a heating pad (37.0 ± 1.5°) with anesthesia maintained (1.5 - 3% isoflurane in 2 NO 2 :1 O 2 ) via a nose cone.…”

Section: Methods Detailsmentioning

confidence: 99%

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An implantable helmet for studying repeat TBI

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Section: Methods Validationmentioning

confidence: 90%

Section: Methods Detailsmentioning

confidence: 99%

An implantable helmet for studying repeat TBI

et al. 2020

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“…Assessment of probe performance using this subdivided zonal pattern revealed CCI-injured rats spent significantly less percentage of time in the outer ring, inner ring and platform during the total 60 second testing period. Similar analysis strategies using subdivided regions of the target quadrant have been utilized to help provide greater resolution of swim patterns and search strategies utilized by the subjects during the task [ 48 - 51 ].…”

Section: Discussionmentioning

confidence: 99%

Reductions in Synaptic Vesicle Glycoprotein 2 Isoforms in the Cortex and Hippocampus in a Rat Model of Traumatic Brain Injury

Fronczak

Henchir

et al. 2021

Mol Neurobiol

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Traumatic brain injury (TBI) can produce lasting cognitive, emotional, and somatic difficulties that can impact quality of life for patients living with an injury. Impaired hippocampal function and synaptic alterations have been implicated in contributing to cognitive difficulties in experimental TBI models. In the synapse, neuronal communication is facilitated by the regulated release of neurotransmitters from docking presynaptic vesicles. The synaptic vesicle glycoprotein 2 (SV2) isoforms SV2A and SV2B play central roles in the maintenance of the readily releasable pool of vesicles and the coupling of calcium to the N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex responsible for vesicle docking. Recently, we reported the findings of TBI-induced reductions in presynaptic vesicle density and SNARE complex formation; however, the effect of TBI on SV2 is unknown. To investigate this, rats were subjected to controlled cortical impact (CCI) or sham control surgery. Abundance of SV2A and SV2B were assessed at 1, 3, 7 and 14 days post-injury by immunoblot. SV2A and SV2B were reduced in the cortex at several time points and in the hippocampus at every time point assessed. Immunohistochemical staining and quantitative intensity measurements completed at 14 days post-injury revealed reduced SV2A immunoreactivity in all hippocampal subregions and reduced SV2B immunoreactivity in the molecular layer after CCI. Reductions in SV2A abundance and immunoreactivity occurred concomitantly with motor dysfunction and spatial learning and memory impairments in the 2 weeks post-injury. These findings provide novel evidence for the effect of TBI on SV2 with implications for impaired neurotransmission neurobehavioral dysfunction after TBI.

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“…To test the hypothesis that electrophysiology can be used as a biomarker for injury severity, EEG and LFP must be compared across multiple injury severities and injury. Specifically, it is important that future studies consider the relationship of theta oscillations to outcome in specific clinically relevant models of mTBI, such as the closed head impact model of engineered rotational acceleration [CHIMERA; (116)], models employing a helmet (117), awake closed head injury (ACHI) models (118)(119)(120), and other models of more diffuse (121,122) or focal injury (123). For a biomarker to have translational relevance, it should be able to identify changes related to initial injury severity, as well as the associated behavioral phenotype.…”

Section: Mild or Moderate Injurymentioning

confidence: 99%

Recovery of Theta Frequency Oscillations in Rats Following Lateral Fluid Percussion Corresponds With a Mild Cognitive Phenotype

et al. 2020

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Whether from a fall, sports concussion, or even combat injury, there is a critical need to identify when an individual is able to return to play or work following traumatic brain injury (TBI). Electroencephalogram (EEG) and local field potentials (LFP) represent potential tools to monitor circuit-level abnormalities related to learning and memory: specifically, theta oscillations can be readily observed and play a critical role in cognition. Following moderate traumatic brain injury in the rat, lasting changes in theta oscillations coincide with deficits in spatial learning. We hypothesized, therefore, that theta oscillations can be used as an objective biomarker of recovery, with a return of oscillatory activity corresponding with improved spatial learning. In the current study, LFP were recorded from dorsal hippocampus and anterior cingulate in awake, behaving adult Sprague Dawley rats in both a novel environment on post-injury days 3 and 7, and Barnes maze spatial navigation on post-injury days 8–11. Theta oscillations, as measured by power, theta-delta ratio, peak theta frequency, and phase coherence, were significantly altered on day 3, but had largely recovered by day 7 post-injury. Injured rats had a mild behavioral phenotype and were not different from shams on the Barnes maze, as measured by escape latency. Injured rats did use suboptimal search strategies. Combined with our previous findings that demonstrated a correlation between persistent alterations in theta oscillations and spatial learning deficits, these new data suggest that neural oscillations, and particularly theta oscillations, have potential as a biomarker to monitor recovery of brain function following TBI. Specifically, we now demonstrate that oscillations are depressed following injury, but as oscillations recover, so does behavior.

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A new model of repeat mTBI in adolescent rats

Cited by 11 publications

References 58 publications

An implantable helmet for studying repeat TBI

An implantable helmet for studying repeat TBI

Reductions in Synaptic Vesicle Glycoprotein 2 Isoforms in the Cortex and Hippocampus in a Rat Model of Traumatic Brain Injury

Recovery of Theta Frequency Oscillations in Rats Following Lateral Fluid Percussion Corresponds With a Mild Cognitive Phenotype

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