Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
J Neurol Sci. 2024 Sep 15;464:123159. doi: 10.1016/j.jns.2024.123159. Epub 2024 Jul 29.
Activation of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a moderating factor between obesity and cognitive impairment in animals, but this has never been tested in humans following mild traumatic brain injury (mTBI). This is a retrospective cohort analysis of subjects enrolled at a single level 1 trauma center (n = 172). Participants completed Trail Making Test Part A and B (TMT-A and B) at six- and twelve-months, Blood samples were obtained within 24 h of mTBI and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, interleukin-18 (IL-18), and IL-1β were assayed. Obese participants (BMI = 30-34.9) were associated with higher IL-18 (p = 0.03) and IL-1β (p = 0.05) and severely obese participants (BMI > 35.0) were associated with higher IL-1β (p = 0.005) than healthy weight participants. IL-1β was associated with TMT-A at six- (p = 0.01) and twelve-months (p = 0.03) and TMT-B at twelve-months (p = 0.046). The interaction of severely obese BMI and IL-1β was associated with TMT-B at six- (p = 0.049) and twelve-months (p = 0.02). ASC (p = 0.03) and the interaction of ASC with severely obese BMI was associated with TMTB at six- (p = 0.02) and twelve-months (p = 0.02). Obesity may augment acute inflammasome response to mTBI and influence worse long-term cognitive outcomes up to one-year post-injury.
NOD 样受体家族 pyrin 域包含 3(NLRP3)炎性小体的激活是动物肥胖和认知障碍之间的调节因素,但在轻度创伤性脑损伤(mTBI)后,这从未在人类中得到过测试。这是一项在单个 1 级创伤中心(n=172)入组的受试者的回顾性队列分析。参与者在 6 个月和 12 个月时完成了连线测试 A 和 B(TMT-A 和 B),在 mTBI 后 24 小时内获得了血液样本,并测定了凋亡相关斑点样蛋白包含半胱氨酸蛋白酶募集域(ASC)、半胱天冬酶-1、白细胞介素-18(IL-18)和白细胞介素-1β。肥胖参与者(BMI=30-34.9)与更高的 IL-18(p=0.03)和 IL-1β(p=0.05)相关,而严重肥胖参与者(BMI>35.0)与更高的 IL-1β(p=0.005)相关与健康体重参与者相比。IL-1β与 6 个月时的 TMT-A(p=0.01)和 12 个月时的 TMT-A(p=0.03)和 12 个月时的 TMT-B(p=0.046)相关。严重肥胖 BMI 和 IL-1β的相互作用与 6 个月时的 TMT-B(p=0.049)和 12 个月时的 TMT-B(p=0.02)相关。ASC(p=0.03)和 ASC 与严重肥胖 BMI 的相互作用与 6 个月时的 TMTB(p=0.02)和 12 个月时的 TMTB(p=0.02)相关。肥胖可能会增强 mTBI 后急性炎性小体的反应,并影响受伤后长达一年的长期认知结果。