Department of Cell Biology and Neuroscience, Rowan-Virtua School of Translational Biomedical Engineering and Sciences, 42 East Laurel Road, Suite 2200, Stratford, NJ 08084, USA.
Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 W. Queen Lane, Philadelphia, PA 19129, USA.
Behav Brain Res. 2025 Jan 5;476:115244. doi: 10.1016/j.bbr.2024.115244. Epub 2024 Sep 4.
Head trauma often impairs cognitive processes mediated within the prefrontal cortex (PFC), leading to impaired decision making and risk-taking behavior. Mild traumatic brain injury (mTBI) accounts for approximately 80 % of reported head injury cases. Most neurological symptoms of a single mTBI are transient; however, growing evidence suggests that repeated mTBI (rmTBI) results in more severe impairments that worsen with each subsequent injury. Although mTBI-induced disruption of risk/reward decision making has been characterized, the potential for rmTBI to exacerbate these effects and the neural mechanisms involved are unknown. Catecholamine neurotransmitters, dopamine (DA) and norepinephrine (NE), modulate PFC-mediated functions. Imbalances in catecholamine function have been associated with TBI and may underlie aberrant decision making. We used a closed head-controlled cortical impact (CH-CCI) model in rats to evaluate the effects of rmTBI on performance of a probabilistic discounting task of risk/reward decision making behavior and expression levels of catecholamine regulatory proteins within the PFC. RmTBI produced transient increases in risky choice preference in both male and female rats, with these effects persisting longer in females. Additionally, rmTBI increased expression of the catecholamine synthetic enzyme, tyrosine hydroxylase (TH), within the orbitofrontal (OFC) region of the PFC in females only. These results suggest females are more susceptible to rmTBI-induced disruption of risk/reward decision making behavior and dysregulation of catecholamine synthesis within the OFC. Together, using the CH-CCI model of rodent rmTBI to evaluate the effects of multiple insults on risk-taking behavior and PFC catecholamine regulation begins to differentiate how mTBI occurrences affect neuropathological outcomes across different sexes.
颅脑创伤常损害前额叶皮层（PFC）介导的认知过程，导致决策受损和冒险行为增加。轻度创伤性脑损伤（mTBI）约占报告的颅脑损伤病例的 80%。大多数单次 mTBI 的神经症状是短暂的；然而，越来越多的证据表明，重复 mTBI（rmTBI）会导致更严重的损伤，且随着每次后续损伤而恶化。尽管已经描述了 mTBI 诱导的风险/回报决策中断，但 rmTBI 加剧这些影响的潜力以及涉及的神经机制尚不清楚。儿茶酚胺神经递质，多巴胺（DA）和去甲肾上腺素（NE），调节 PFC 介导的功能。儿茶酚胺功能失衡与 TBI 有关，可能是异常决策的基础。我们使用大鼠闭合性颅脑损伤（CH-CCI）模型来评估 rmTBI 对风险/回报决策行为的概率折扣任务表现和 PFC 中儿茶酚胺调节蛋白表达水平的影响。rmTBI 导致雄性和雌性大鼠的风险选择偏好短暂增加，而雌性大鼠的这些影响持续时间更长。此外，rmTBI 仅在雌性大鼠的眶额（OFC）区域 PFC 中增加了儿茶酚胺合成酶酪氨酸羟化酶（TH）的表达。这些结果表明，雌性大鼠更容易受到 rmTBI 诱导的风险/回报决策行为中断和 OFC 中儿茶酚胺合成失调的影响。总之，使用啮齿动物 rmTBI 的 CH-CCI 模型评估多次损伤对冒险行为和 PFC 儿茶酚胺调节的影响，开始区分 mTBI 发生如何影响不同性别之间的神经病理学结果。
