Ultra-endurance (UE) race has been associated with brain metabolic changes, but it is still unknown which regions are vulnerable. This study investigated whether high-volume training in rodents, even under moderate intensity, can induce cerebellar oxidative and inflammatory status. Forty-five adult rats were divided into six groups according to a training period, followed or not by an exhaustion test (ET) that simulated UE: control (C), control + ET (C-ET), moderate-volume (MV) training and MV-ET, high-volume training (HV) and HV-ET. The training period was 30 (MV) and 90 (HV) min/day, 5 times/week for 3 months as a continuous running on a treadmill at a maximum velocity of 12 m/min. After 24 h, the ET was performed at 50% maximum velocities up to the animals refused to run, and then serum lactate levels were evaluated. Serum and cerebellar homogenates were obtained 24 h after ET. Serum creatine kinase (CK), lactate dehydrogenase (LDH), and corticosterone levels were assessed. Lipid peroxidation (LP), nitric oxide (NO), Interleukin 1β (IL-1β), and GFAP proteins, reduced and oxidized glutathione (GSH and GSSG) levels, superoxide dismutase (SOD) and catalase (CAT) activities were quantified in the cerebellum. Serum lactate concentrations were lower in MV-ET (∼20%) and HV-ET (∼40%) compared to the C-ET group. CK and corticosterone levels were increased more than ∼ twofold by HV training compared to control. ET increased CK levels in MV-ET vs. MV group (P = 0.026). HV induced higher LP levels (∼40%), but an additive effect of ET was only seen in the MV-ET group (P = 0.02). SOD activity was higher in all trained groups vs. C and C-ET (P < 0.05). CAT activity, however, was intensified only in the MV group (P < 0.02). The 50 kDa GFAP levels were enhanced in C-ET and MV-ET vs. respective controls, while 42 kDa (∼40%) and 39 kDa (∼26%) isoform levels were reduced. In the HV-ET group, the 50 KDa isoform amount was reduced ∼40–60% compared to the other groups and the 39 KDa isoform, increased sevenfold. LDH levels, GSH/GSSG ratio, and NO production were not modified. ET elevated IL-1β levels in the CT and MV groups. Data shows that cerebellar resilience to oxidative damage may be maintained under moderate-volume training, but it is reduced by UE running. High-volume training per se provoked systemic metabolic changes, cerebellar lipid peroxidation, and unbalanced enzymatic antioxidant resource. UE after high-volume training modified the GFAP isoform profile suggesting impaired astrocyte reactivity in the cerebellum.

超耐力（UE）竞赛与大脑代谢变化有关，但尚不清楚哪些区域容易受到影响。这项研究调查了啮齿类动物的高容量训练（即使是中等强度）是否可以诱导小脑氧化和炎症状态。45只成年大鼠根据训练周期分为六组，随后或不进行模拟UE的力竭试验（ET）：对照组（C）、对照组+ET（C-ET）、中等训练量（MV）训练和 MV-ET、大容量训练 (HV) 和 HV-ET。训练时间为30（MV）和90（HV）分钟/天，每周5次，持续3个月，在跑步机上以最大速度12 m/min连续跑步。24小时后，以50%最大速度进行ET直至动物拒绝奔跑，然后评估血清乳酸水平。ET后24小时获得血清和小脑匀浆。评估血清肌酸激酶（CK）、乳酸脱氢酶（LDH）和皮质酮水平。脂质过氧化 (LP)、一氧化氮 (NO)、白细胞介素 1β (IL-1β) 和 GFAP 蛋白、还原型和氧化型谷胱甘肽（GSH 和 GSSG）水平、超氧化物歧化酶 (SOD) 和过氧化氢酶 (CAT) 活性在小脑。与 C-ET 组相比，MV-ET (∼20%) 和 HV-ET (∼40%) 的血清乳酸浓度较低。与对照组相比，HV 训练后的 CK 和皮质酮水平增加约两倍以上。与 MV 组相比，ET 增加 MV-ET 中的 CK 水平（磷= 0.026）。HV 诱导较高的 LP 水平（~40%），但 ET 的相加效应仅在 MV-ET 组中可见（磷= 0.02）。所有训练组中的 SOD 活性均高于 C 组和 C-ET 组（磷< 0.05）。然而，CAT 活性仅在 MV 组中增强（磷< 0.02）。与各自的对照相比，C-ET 和 MV-ET 中的 50 kDa GFAP 水平有所增强，而 42 kDa (∼40%) 和 39 kDa (∼26%) 亚型水平则降低。在 HV-ET 组中，与其他组相比，50 KDa 异构体的量减少了约 40-60%，而 39 KDa 异构体的量增加了七倍。LDH 水平、GSH/GSSG 比率和 NO 产生未改变。ET 升高 CT 组和 MV 组中的 IL-1β 水平。数据显示，在中等训练量的训练下，小脑对氧化损伤的抵抗力可能得以维持，但 UE 跑步会降低小脑对氧化损伤的抵抗力。大容量训练本身引发全身代谢变化、小脑脂质过氧化和酶抗氧化资源不平衡。大容量训练后的 UE 改变了 GFAP 亚型图谱，表明小脑中的星形胶质细胞反应性受损。