BACKGROUND:To the best of our knowledge, few studies have analyzed the effects of hypoxic brain injury on seizure susceptibility and pathophysiological mechanisms underlying seizure susceptibility following hypoxic brain injury. OBJECTIVE: To investigate changes in seizure susceptibility and neuronal loss, as well as expression of vesicular glutamate transporter subtype 1(VGluT1), following hypoxic cerebral insult. DESIGN, TIME AND SETTING: A randomized controlled animal experiment was performed in the Department of Neurology, The Second Affiliated Hospital, Chongqing Medical University, between May 2006 and September 2007. MATERIALS: Seventy, male, Sprague Dawley rats, weighing 230–270 g, were used in the present study. Pentylenetetrazol (PTZ) was purchased from Sigma. Mouse NeuN monoclonal antibody and rabbit VGluT-1 polyclonal antibody were purchased from Chemicon and Gene Tex, respectively. METHODS: Rats were randomly assigned to control and hypoxia groups (n = 35 for each group). Hypoxia was induced in rats using 8% oxygen-nitrogen gas mixture. Control rats were subjected to the same procedures, but with exposure to room air. MAIN OUTCOME MEASURES: Rats (n = 15 for each group) received intraperitoneal injections of PTZ, a sub-convulsive dose of 35 mg/kg/2 d for 20 days. The success of model establishment, as well as seizure scales, was measured. Rats from both groups, which were successfully kindled with PTZ, were divided into simple kindling and post-hypoxic kindling, respectively. A separate group, including rats from simple kindling and post-hypoxic kindling, was studied for neuronal loss and VGluT1 expression in the temporal cortex, midbrain, and hippocampal CA1 subfield using immunohistochemistry and western blot techniques, respectively. RESULTS: Seventy rats were included in the final analysis. (1)Compared with control animals (n = 7), seizure scales were greater in hypoxic rats (n = 11), which indicates that post-hypoxic rats reacted more sensitive to kindling. (2)The average number of neurons within the temporal cortex, midbrain, and hippocampal CA1 subfield was less in hypoxic rats than in control rats. After comparing post-hypoxia kindling with simple kindling, both the temporal cortex and hippocampal CA1 subfield exhibited obvious neuronal loss in the post-hypoxic kindling group (P < 0.05). (3)Compared with hypoxia and simple kindling, the number of VGluT1 immunopositive cells was greater in the post-hypoxic kindling group (P < 0.05). CONCLUSION: Hypoxic brain injury leads to increased seizure susceptibility, neuronal loss, and enhanced of VGluT1 expression. BACKGROUND: To the best of our knowledge, few studies have analyzed the effects of hypoxic brain injury on seizure susceptibility and pathophysiological mechanisms underlying seizure susceptibility following hypoxic brain injury. OBJECTIVE: To investigate changes in seizure susceptibility and neuronal loss, as well as expression of THE TIME AND SETTING: A randomized controlled animal experiment was performed in the Department of Neurology, The Second Affiliated Hospital, Chongqing Medical University, between May 2006 and September 2007. MATERIALS (VGluT1) Pentylenetetrazol (PTZ) was purchased from Sigma. Mouse NeuN monoclonal antibody and rabbit VGluT-1 polyclonal antibody were purchased from Chemicon and Gene Tex, respectively. METHODS: Rats were randomly assigned to control and hypoxia groups (n = 35 for each group) Hypoxia was induced in rats using 8% oxygen-nitrogen gas mixture. Control rats were subjected to the same procedures, but with exposure to room air. MAIN OUTCOME MEASURES: Rats (n = 15 for each group) received intraperitoneal injections of PTZ, The success of model establishment, as well as seizure scales, was measured. Rats from both groups, which were successfully kindled with PTZ, were divided into simple kindling and A separate group, including rats from simple kindling and post-hypoxic kindling, was studied for neuronal loss and VGluT1 expression in the temporal cortex, midbrain, and hippocampal CA1 subfield using immunohistochemistry and western blot techniques, respectively. RESULTS: Seventy rats were included in the final analysis. (1) Compared with control animals (n = 7), seizure scales were greater in hypoxic rats (n = 11), which indicates that post- k(2) The average number of neurons within the temporal cortex, midbrain, and hippocampal CA1 subfield was less in hypoxic rats than in control rats. Both were compared post-hypoxia kindling with simple kindling, both on the temporal cortex and hippocampal CA1 subfield show (3) Compared with hypoxia and simple kindling, the number of VGluT1 immunopositive cells was greater in the post-hypoxic kindling group (P <0.05). CONCLUSION: Hypoxic brain injury leads to increased seizure susceptibility, neuronal loss, and enhanced of VGluT1 expression.