Gabriel E M, Inglefield J R, Chadwick L E, Schwartz-Bloom R D
Department of Surgery (Division of Neurosurgery), Duke University Medical Center, Durham, NC 27710, USA.
Brain Res. 1998 Mar 2;785(2):279-86. doi: 10.1016/s0006-8993(97)01415-7.
The septo-hippocampal pathway contains a major gamma-aminobutyric acid (GABA) projection to dendritic fields within the hippocampus. To determine the importance of the septo-hippocampal pathway in ischemia-induced accumulation of GABA and subsequent cell death in area CA1 of hippocampus, septo-hippocampal deafferentation of adult gerbils was performed. Electrolytic lesions were produced in the medial or medial plus lateral septal regions in gerbils 7 days prior to being subjected to 5 min forebrain ischemia. The extent of deafferentation of the dorsal hippocampus was determined histochemically by acetylcholinesterase staining. Both the medial and medial plus lateral septal lesions produced nearly complete loss of acetylcholinesterase staining in the dorsal hippocampus indicating relatively complete deafferentation. During and following ischemia, in vivo microdialysis was used to measure extracellular GABA accumulation, which reached concentrations up to 1060 +/- 143% of basal. Septo-hippocampal deafferentation in both groups of lesioned animals failed to prevent the accumulation of GABA (and glutamate) induced by ischemia, indicating that ischemia-induced GABA accumulation in area CA1 arises principally from intrinsic GABAergic interneurons. Ischemic animals with medial septal lesions did not demonstrate neuroprotection or increased damage in the stratum pyramidale 7 days after reperfusion. Since the septo-hippocampal pathway provides the source of GABAergic disinhibition within the hippocampus, neither disinhibition nor the septo-hippocampal input appear to play an important role in the development of ischemia-induced neuronal death in the hippocampus.
隔海马通路包含一条主要的γ-氨基丁酸（GABA）投射纤维，其投射至海马内的树突野。为了确定隔海马通路在缺血诱导的海马CA1区GABA蓄积及随后的细胞死亡中的重要性，对成年沙鼠进行了隔海马去传入实验。在沙鼠接受5分钟前脑缺血前7天，对其内侧或内侧加外侧隔区进行电解损伤。通过乙酰胆碱酯酶染色组织化学法确定背侧海马的去传入程度。内侧和内侧加外侧隔区损伤均导致背侧海马乙酰胆碱酯酶染色几乎完全丧失，表明去传入相对完全。在缺血期间及之后，采用体内微透析法测量细胞外GABA蓄积，其浓度达到基础值的1060±143%。两组损伤动物的隔海马去传入均未能阻止缺血诱导的GABA（和谷氨酸）蓄积，这表明缺血诱导的海马CA1区GABA蓄积主要源于内在的GABA能中间神经元。内侧隔区损伤的缺血动物在再灌注7天后，在锥体层未表现出神经保护作用或损伤增加。由于隔海马通路是海马内GABA能去抑制的来源，去抑制和隔海马输入似乎在海马缺血诱导的神经元死亡的发生中均未发挥重要作用。
