A Mouse Model of Temporal Lobe Contusion

Authors

J Marc Simard, Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Cigdem Tosun, Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Orest Tsymbalyuk, Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Mitchell Moyer, Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Kaspar Keledjian, Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Natalya Tsymbalyuk, Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Adedayo Olaniran, Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Madison Evans, Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Jenna Langbein, Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Ziam Khan, Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Matthew Kreinbrink, Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Prajwal Ciryam, Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Jesse A. Stokum, Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Ruchira M. Jha, Department of Neurology, Barrow Neurological Institute and St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
Alexander Ksendzovsky, Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Volodymyr Gerzanich, Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.

Document Type

Article

Abstract

Trauma to the brain can induce a contusion characterized by a discrete intracerebral or diffuse interstitial hemorrhage. In humans, "computed tomography-positive," that is, hemorrhagic, temporal lobe contusions (tlCont) have unique sequelae. TlCont confers significantly increased odds for moderate or worse disability and the inability to return to baseline work capacity compared to intra-axial injuries in other locations. Patients with tlCont are at elevated risks of memory dysfunction, anxiety, and post-traumatic epilepsy due to involvement of neuroanatomical structures unique to the temporal lobe including the amygdala, hippocampus, and ento-/perirhinal cortex. Because of the relative inaccessibility of the temporal lobe in rodents, no preclinical model of tlCont has been described, impeding progress in elucidating the specific pathophysiology unique to tlCont. Here, we present a minimally invasive mouse model of tlCont with the contusion characterized by a traumatic interstitial hemorrhage. Mortality was low and sensorimotor deficits (beam walk, accelerating rotarod) resolved completely within 3-5 days. However, significant deficits in memory (novel object recognition, Morris water maze) and anxiety (elevated plus maze) persisted at 14-35 days and nonconvulsive electroencephalographic seizures and spiking were significantly increased in the hippocampus at 7-21 days. Immunohistochemistry showed widespread astrogliosis and microgliosis, bilateral hippocampal sclerosis, bilateral loss of hippocampal and cortical inhibitory parvalbumin neurons, and evidence of interhemispheric connectional diaschisis involving the fiber bundle in the ventral corpus callosum that connects temporal lobe structures. This model may be useful to advance our understanding of the unique features of tlCont in humans.

Medical Subject Headings

Animals; Disease Models, Animal; Temporal Lobe (injuries, pathology); Mice; Male; Mice, Inbred C57BL; Brain Contusion (pathology, physiopathology)

Publication Date

1-1-2025

Publication Title

Journal of neurotrauma

E-ISSN

1557-9042

Volume

42

Issue

2025-01-02

First Page

143

Last Page

160

PubMed ID

39302058

Digital Object Identifier (DOI)

10.1089/neu.2024.0242

Recommended Citation

Simard, J Marc; Tosun, Cigdem; Tsymbalyuk, Orest; Moyer, Mitchell; Keledjian, Kaspar; Tsymbalyuk, Natalya; Olaniran, Adedayo; Evans, Madison; Langbein, Jenna; Khan, Ziam; Kreinbrink, Matthew; Ciryam, Prajwal; Stokum, Jesse A.; Jha, Ruchira M.; Ksendzovsky, Alexander; and Gerzanich, Volodymyr, "A Mouse Model of Temporal Lobe Contusion" (2025). Neurology. 2001.
https://scholar.barrowneuro.org/neurology/2001