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, Gerzanich Volodymyr
Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
J Neurotrauma. 2025 Jan;42(1-2):143-160. doi: 10.1089/neu.2024.0242. Epub 2024 Oct 14.
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.
脑外伤可引发挫伤，其特征为局灶性脑内出血或弥漫性间质出血。在人类中，“计算机断层扫描阳性”，即出血性颞叶挫伤（tlCont）具有独特的后遗症。与其他部位的轴内损伤相比，tlCont导致中度或更严重残疾以及无法恢复到基线工作能力的几率显著增加。由于颞叶独特的神经解剖结构（包括杏仁核、海马体和内嗅/嗅周皮质）受累，tlCont患者存在记忆功能障碍、焦虑和创伤后癫痫的风险升高。由于啮齿动物的颞叶相对难以触及，尚未描述tlCont的临床前模型，这阻碍了阐明tlCont独特的具体病理生理学的进展。在此，我们提出一种tlCont的微创小鼠模型，其挫伤特征为创伤性间质出血。死亡率较低，感觉运动缺陷（横梁行走、加速旋转棒试验）在3 - 5天内完全恢复。然而，在14 - 35天时，记忆（新物体识别、莫里斯水迷宫试验）和焦虑（高架十字迷宫试验）方面仍存在显著缺陷，并且在7 - 21天时海马体中的非惊厥性脑电图癫痫发作和尖峰活动显著增加。免疫组织化学显示广泛的星形胶质细胞增生和小胶质细胞增生、双侧海马硬化、双侧海马和皮质抑制性小白蛋白神经元缺失，以及涉及连接颞叶结构的胼胝体腹侧纤维束的半球间连接性失联络的证据。该模型可能有助于增进我们对人类tlCont独特特征的理解。
