Reduction of inflammatory responses by L-serine treatment leads to neuroprotection in mice after traumatic brain injury.
This study was designed to evaluate the neuroprotective effect of l-serine and the underlying mechanisms in mice after traumatic brain injury (TBI) induced using a weight drop model. The mice were intraperitoneally injected with l-serine 3 h after TBI and then injected twice each day for 7 days or until the end of the experiment. The neurological severity score, brain water content, lesion volume, and neurone loss were determined. The levels of TNF-α, IL-1β, IL-6, and IL-10 and the number of GFAP- and Iba-1-positive cells and activated caspase-3-positive neurones in the brain tissue ipsilateral to TBI were also measured. Simultaneously, the influences of l-serine on these variables were observed. In addition, the expression of glycine receptors and l-serine-induced currents were measured. We found l-serine treatment: 1) decreased the neurological deficit score, brain water content, lesion volume, and neurone loss; 2) inhibited activated caspase-3; and 3) reduced the levels of TNF-α, IL-1β and IL-6 and the number of GFAP- and Iba-1-positive cells. The effects of l-serine were antagonised by the administration of strychnine, an antagonist of glycine receptors. In addition, we found that glycine receptors were expressed mainly in the cortical neurones but less in the astrocytes or microglial cells, and l-serine activated these receptors and induced strychnine-sensitive currents in these neurones. In conclusion, l-serine induces the activation of glycine receptors, which alleviates neuronal excitotoxicity, a secondary brain injury process, thereby reduces the activation of astrocytes and microglial cells and secretion of proinflammatory cytokines and inhibits neuronal apoptosis. Thus, l-serine treatment leads to neuroprotection of brain tissue through reducing inflammatory responses and improves recovery of the neurological functions in mice after traumatic brain injury.
Department of Neurophysiology and Neuropharmacology, Institute of Nautical Medicine and Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Chongchuan District, Nantong, Jiangsu 226001, China.
Pei-Pei
PP
Zhai
Department of Neurophysiology and Neuropharmacology, Institute of Nautical Medicine and Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Chongchuan District, Nantong, Jiangsu 226001, China.
Li-Hua
LH
Xu
Department of Neurophysiology and Neuropharmacology, Institute of Nautical Medicine and Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Chongchuan District, Nantong, Jiangsu 226001, China.
Juan-Juan
JJ
Yang
Department of Neurophysiology and Neuropharmacology, Institute of Nautical Medicine and Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Chongchuan District, Nantong, Jiangsu 226001, China. Electronic address: jiangzl@ntu.edu.cn.
Zheng-Lin
ZL
Jiang
Department of Neurophysiology and Neuropharmacology, Institute of Nautical Medicine and Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Chongchuan District, Nantong, Jiangsu 226001, China.
Guang-Wei
GW
Zhao
Department of Neurophysiology and Neuropharmacology, Institute of Nautical Medicine and Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Chongchuan District, Nantong, Jiangsu 226001, China.
Li
L
Sun
Department of Neurophysiology and Neuropharmacology, Institute of Nautical Medicine and Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Chongchuan District, Nantong, Jiangsu 226001, China.
Guo-Hua
GH
Wang
Department of Neurophysiology and Neuropharmacology, Institute of Nautical Medicine and Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Chongchuan District, Nantong, Jiangsu 226001, China.
Xia
X
Li
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D001929:Brain Edema / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018684:Glycine Agents / Q000494:pharmacology; D008813:Mice, Inbred ICR; D017628:Microglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D000066829:Neuroprotection / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011897:Random Allocation; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors / Q000378:metabolism; D012694:Serine / Q000494:pharmacology*; D013331:Strychnine / Q000494:pharmacology
D016207:Cytokines; D018684:Glycine Agents; D018696:Neuroprotective Agents; D018009:Receptors, Glycine; D012694:Serine; D013331:Strychnine
Glycine receptor; Inflammatory response; Mouse; Neuroprotection; Traumatic brain injury; l-serine