慢性应激抑郁模型大鼠强迫游泳后海马中HsP70的表达

目的研究慢性应激对强迫游泳大鼠海马神经元热休克蛋白70(Hsp70)表达的影响。方法将50 只大鼠随机分为实验组和对照组各25只。实验组大鼠通过21天的应激刺激制作抑郁动物模型,此期间对照组大 鼠正常饲养。此后所有大鼠逐只进行急性强迫应激刺激。采用特异性抗体的免疫组织化学方法,观察2组大鼠在 强迫游泳后2 h、6 h、18 h、24 h和48 h各时点海马神经元Hsp70的表达情况。结果慢性应激抑郁大鼠模型接受 急性强迫游泳应激后,海马CA3区和齿状回(DG)内Hsp70蛋白的表达较对照组强迫游泳后显著降低(P<0．05)。 结论慢性应激使大鼠在急性强迫游泳应激后海马CA3区和DG内Hsp70的表达降低。     

慢性应激抑郁模型大鼠强迫游泳后海马中c-fos的表达

目的 研究慢性应激对强迫游泳大鼠海马神经元c-fos表达的影响。方法 采用特异性抗体的免疫组织化学方法,在大鼠慢性应激抑郁模型基础上,观察急性强迫游泳应激后海马神经元c-fos的表达情况。结果 抑郁模型大鼠接受急性强迫游泳应激后,海马CA3区和齿状回(DG)内FOS蛋白的表达在各主要时点均比对照组降低,图像分析提示,上述两区域的FOS阳性神经元对应切面面积比明显降低(P<0.05),平均目标灰度值显著增加(P<0.05)。结论 慢性应激使大鼠在急性强迫游泳应激后海马CA3区和DG内c-fos的表达降低。     

癫痫持续发作对大鼠海马神经元的影响

目的 研究实验性癫痫大鼠在癫痫发作持续不同时间对海马神经元的影响。方法24只SD大鼠随机分成4组：诱发火鼠瘢痫持续状态（status cpilepticus，SE）〈10、10～30、〉30min组及正常对照组。于电镜下观察各组海马神经元超微结构变化；采用免疫组化方法检测凋亡相关基因bcl-2、bax的蛋白表达及通过流式细胞技术检测细胞凋亡情况。结果SE〈10min组海马神经元所受影响不大．SE10～30min组海马神经元具有明显凋亡特征．SE〉30min组多数海马神经元呈坏死性改变。结论大鼠SE对海马神经元损伤有凋亡和坏死两种不同形式．这与癫痫发作的持续时间密切相关。     

文拉法辛对慢性应激抑郁大鼠海马区可塑性相关蛋白mRNA表达的影响

目的 观察文拉法辛对慢性应激抑郁大鼠海马区可塑性相关蛋白mRNA表达的影响.方法 用慢性不可预见应激(CUS)方法建立大鼠抑郁模型,给予2种剂量(5 mg/kg体质量和10 mg/kg体质量)的抗抑郁剂文拉法辛,用反转录-聚合酶链反应检测大鼠海马区脑源性神经营养因子(BDNF)、转录因子环磷腺苷反应元件结合蛋白(CREB)及神经细胞黏附分子(NCAM)mRNA表达的变化.正常对照组、抑郁模型组、抑郁模型后注射生理盐水14 d组及28 d组各10只,抑郁模型后小剂量文拉法辛(5 mg/kg体质量)治疗14 d组及28 d组、抑郁模型后大剂量文拉法辛(10 mg/kg体质量)治疗14 d组及28 d组各11只.结果 抑郁模型大鼠体质量、蔗糖水消耗量及旷场实验结果均明显低于正常对照组,提示抑郁模型大鼠在第28天建立成功.慢性不可预见应激28 d后,抑郁模型大鼠海马区BDNF(0.18±0.09)、CREB(0.10±0.05)及NCAM(0.08±0.04)mRNA表达水平均明显低于正常组[吸光度比值分别为(0.41±0.12)、(0.26±0.05)及(0.24±0.08);P均＜0.05 ].5 mg/kg体质量文拉法辛明显增加海马区3种可塑性相关蛋白mRNA的表达;10 mg/kg文拉法辛轻度降低海马区3种可塑性相关蛋白mRNA的表达.结论 文拉法辛在一定剂量范围内调节海马区的神经可塑性,BDNF、CREB及NCAM在抑郁症的病因及治疗中发挥重要作用.     

慢性冷水游泳应激对大鼠海马、前脑皮层神经颗粒素含量的影响

目的探讨慢性应激对大鼠海马和前脑皮层神经颗粒素(NG)含量的影响。方法将雄性SD大鼠随机分为应激组(予10℃冷水游泳应激,共2周)、装置对照组和正常对照组,每组10只。于应激前后测量三组大鼠的体质量变化情况,并记录每天应激过程中应激组和装置对照组的排便量以考察应激的强度,应激后以Westernblotting方法测定海马和前脑皮层中的NG含量(以NG含量与βActin含量的比值表示)。结果(1)应激前后,三组大鼠的体质量比较,差异均无统计学意义(P>0.05),但应激组的体质量增长相对缓慢;(2)应激第4—14天应激组的排便量多于装置对照组(P<0.01);(3)应激组和装置对照组海马的NG含量[分别为(0.66±0.13)和(0.94±0.26)]低于正常对照组[(1.93±0.53)],差异有统计学意义(P<0.01);(4)应激组前脑皮层的NG含量[(0.45±0.00)]低于装置对照组和正常对照组[分别为(2.76±1.74)和(2.87±1.63)],差异有统计学意义(P<0.01);(5)应激组海马NG含量高于前脑皮层(P<0.01);装置对照组海马NG含量低于前脑皮层(P<0.01);正常对照组海马与前脑皮层NG含量的差异无统计学意义。结论慢性应激导致海马和前脑皮层NG含量显著下降;对于时程长、程度严重、适应不良的冷水游泳应激,前脑皮层受损比海马更为严重;而对于时程长、程度微弱的装置应激,海马则比前脑皮层更为敏感。     

缺氧-复氧对大鼠海马培养神经元Bcl-2、Bax表达和神经元凋亡的影响

目的 观察缺氧-复氧对体外培养海马神经元Bcl-2和Bax表达和神经元凋亡的影响。方法 取培养12d的海马神经元，置于恒温(36℃)密闭容器内，连续充以无氧气体[90％(体积分数)N2、10％(体积分数)CO2]，在缺氧条件下继续培养4h后，再于常氧培养箱内复氧培养24h和72h。于不同时间观察神经元存活数，并分别用抗Bcl-2和Bax抗血清进行免疫组织化学染色，观察缺氧-复氧后大鼠海马培养神经元Bcl-2和Bax表达。并用原位末端标记(TUNEL)法和流式细胞术分别检测缺氧-复氧对体外培养海马神经元凋亡的影响。结果 缺氧-复氧后24～72h,海马神经元对Bcl-2的表达逐渐减弱，对Bax的表达逐渐增强，对Bax／Bcl-2比值逐渐增大，凋亡神经元百分率逐渐增多。结论 缺氧-复氧后24～72h神经元凋亡的发生与神经元Bcl-2表达逐渐减弱，Bax表达逐渐增强，Bax／Bcl-2比值逐渐增大有关。     

多氯联苯对大鼠海马c-fos表达的研究

多氯联苯 (polychlorinated biphenyl,PCB)结构类似于甾体类激素能竞争该类激素的受体发挥一定生物功能。此研究通过 PCB是否对大鼠海马结构和功能产生影响 ,以了解 PCB对学习、记忆功能的影响。1　材料和方法　选用 Wistar雌性大鼠 2 4只 ,随机分为 4组。分别饲喂含质量分数 1× 1 0 1 2 、1× 1 0 1 1 、1× 1 0 1 0 PCB饲料及正常饲料。1个后进行交配、受孕、分娩。断乳后的仔鼠分别选取体重近似的雄性大鼠 1 0只 ,对应饲喂相应的饲料 ,3个月后断头处死 ,分离海马并以 4g/ L多聚甲醛固定待测。海马标本常规 HE染色 ,免疫组化 ABC…     

万拉法新对强迫游泳大鼠下丘脑和海马c-fos及c-jun蛋白表达的下调作用

目的　探索新一代抗抑郁药万拉法新对大鼠下丘脑和海马内ｃｆｏｓ 和ｃｊｕｎ 蛋白表达的影响。方法　采用特异性抗体的原位免疫细胞化学方法,在强迫游泳大鼠抑郁模型上,观察万拉法新慢性给药（ 腹腔内注射每日１ 次,连续７ 次）对大鼠游泳不动时间和下丘脑及海马核团ｃｆｏｓ 和ｃｊｕｎ 表达的影响;用图像分析技术对大鼠下丘脑室旁核（ Ｐ Ｖ Ｎ） 、视上核（ Ｓ Ｏ Ｎ） 和海马齿状回（ Ｄ Ｇ） 内的ｆｏｓ 和ｊｕｎ 阳性细胞的相对切面面积比和平均目标灰度进行分析。结果　强迫游泳可使大鼠下丘脑和海马内多个核团的ｃｆｏｓ 和ｃｊｕｎ 蛋白表达水平增加,而万拉法新明显缩短了强迫游泳大鼠的不动时间。图像分析结果提示,万拉法新使强迫游泳大鼠下丘脑 Ｐ Ｖ Ｎ 和 Ｓ Ｏ Ｎ 及海马 Ｄ Ｇ 内ｆｏｓ 和ｊｕｎ 阳性细胞相对切面面积比明显降低（ Ｐ＜００５） ,而平均目标灰度显著增加（ Ｐ＜ ００１） 。结论　下丘脑 Ｐ Ｖ Ｎ、 Ｓ Ｏ Ｎ 和海马 Ｄ Ｇ 可能是介导抗抑郁药抑制大鼠绝望行为的重要中枢核团,ｆｏｓ 和ｊｕｎ 蛋白可能是抗抑郁药发挥受体后作用的传导物质。     

红藻氨酸致惊大鼠海马神经元Caspase—3表达与神经元凋亡

目的：研究Caspase-3在红藻氨酸（Kainate,KA)致惊大鼠海马中的变化及其在海马神经元凋亡中的作用。方法：在KA所致大鼠惊厥模型中，用免疫组织化学方法检测惊厥后不同时间点大鼠海马中Caspase-3的表达，用电子显微镜和原位末端标记法（TUNEL）检测惊厥后不同时间点大鼠海马神经元凋亡。结果：惊厥后1d,大鼠海马内Caspase-3的表达就明显升高，一直持续到惊厥3d；大鼠海马内凋亡细胞从惊厥后3d即明显增多，一直持续到惊厥后7d。结论：KA所致惊厥后，大鼠海马内Caspase-3表达明显升高，神经元凋亡明显增多，而且Caspase-3的变化发生在神经元亡增多之前，提示Caspase-3可能参与了KA致惊厥大鼠海马神经元凋亡的发生。     

慢性应激抑郁大鼠海马CA1神经元突触可塑性研究

目的 探讨慢性轻度不可预见应激(chronic unpredictable mild stress,CUMS)抑郁模型大鼠海马CA1区神经元的突触可塑性改变.方法 将20只雄性Sprague-Dawley (SD)大鼠随机等分为CUMS组和对照组,前者连续28天每天随机接受不同的应激,对照组同样条件下饲养但不给应激,至第28天进行行为测评后处死,在日立(H7500)透射电镜下测量海马CA1神经元突触界面结构参数.结果 CUMS抑郁大鼠海马CA1神经元突触活性区长度(216.64±20.19 nm)及突触后致密物厚度(42.4±5.23 nm)显著小于对照组(321.58±12.27nm,69.6±4.77 nm),差异有统计学意义(P＜0.05),突触界面曲率及宽度与对照组差异无统计学意义(P＞0.05).结论 慢性应激性抑郁大鼠存在海马CA1区神经元突触可塑性的改变.这提示抑郁症的发病机制可能与海马神经元突触可塑性相关.     

Prenatal stress in rats predicts immobility behavior in the forced swim test. Effects of a chronic treatment with tianeptine

Prenatally-stressed (PS) rats are characterized by a general impairment of the hypothalamo-pituitary-adrenal (HPA) axis and sleep disturbances indicating that this model has face validity with some clinical features observed in a subpopulation of depressed patients. The prolonged corticosterone secretion shown by PS rats in response to stress was positively correlated with an increased immobility behavior in the forced swim test. To investigate the predictive validity of this model, a separate group of animals was chronically treated with the antidepressant tianeptine (10 mg/kg i.p. for 21 days). Such chronic treatment reduced in PS rats immobility time in the forced swim test. These findings suggest that the PS rat is an interesting animal model for the evaluation of antidepressant treatment.     

Influence of immobilization and forced swim stress on the neurotoxicity of lambda-cyhalothrin in rats: Effect on brain biogenic amines and BBB permeability

Experimental studies have been carried out on rats to understand the influence of immobilization stress (IMS), a psychological stressor and forced swim stress (FSS), a physical stressor in the neurotoxicity of lambda-cyhalothrin (LCT), a new generation type II synthetic pyrethroid with extensive applications. No significant change in plasma corticosterone levels and blood brain barrier (BBB) permeability was observed in rats subjected to IMS (one session of 15 min/day), FSS (one session of 3 min/day) for 28 days or LCT treatment (3.0 mg/kg body weight, p.o. suspended in groundnut oil) for 3 days (26th, 27th and 28th day) as compared to controls. Marginal changes in the levels of biogenic amines and their metabolites (NE, EPN, DA, HVA, DOPAC, 5-HT) in hypothalamus, frontal cortex, hippocampus, and corpus striatum were observed in rats subjected to IMS or FSS or LCT alone as compared to controls. It was interesting to note that pre-exposure to IMS or FSS followed by LCT treatment for 3 days caused a marked increase in plasma corticosterone levels associated with disruption in the BBB permeability as compared to rats exposed to IMS or FSS or LCT alone. Pre-exposure to IMS or FSS followed by LCT treatment for 3 days resulted to alter the levels of biogenic amines and their metabolites in hypothalamus, frontal cortex, hippocampus, and corpus striatum as compared to rats exposed to IMS or FSS or LCT alone. Although neurochemical changes were more intense in rats pre-exposed to IMS as compared to those subjected to FSS on LCT treatment, the results indicate that both psychological and physical stress could be important influencing factors in the neurotoxicity of LCT.     

Antidepressant-like effects of acute and chronic treatment with zinc in forced swim test and olfactory bulbectomy model in rats

The activity of zinc administered intraperitoneally, acutely (in single dose), sub-chronically (in triple doses) or chronically (once daily for 14 days) were assessed in the forced swim test (FST) and olfactory bulbectomy (OB) model of depression in rats. Previously, we have demonstrated that acute administration of zinc sulfate is active in FST in rats and mice. In the present study, zinc hydroaspartate in a dose of 65 mg/kg (11.5 mgZn/kg), all: acute, sub-chronic and chronic administration, reduced the immobility time in the FST in rats. Removal of olfactory bulbs (OB surgery) in rats is associated with variety of behavioral abnormalities such as deficit in a step-down passive avoidance or hyperactivity in the "open field" test. Both acute and chronic administration of zinc hydroaspartate reduced the number of trials needed to the learning passive avoidance and reduced the OB-induced hyperactivity in rats. At the time schedule following zinc hydroaspartate administration, when behavioral experiments were performed, the serum zinc concentrations were significantly higher than control-physiological values. These results confirm activity of zinc in the FST, show its antidepressant-like activity in the OB rat model of depression, demonstrate the lack of tolerance to these effects and suggest relationship of these antidepressant-like effects with the rise in serum zinc. These animal data further suggest antidepressant activity of zinc in human depression.     

Exposure to forced swim stress does not alter central production of IL-1

In recent years, there has been increasing recognition that pro-inflammatory cytokines play a role in behavioral and physiological alterations produced by exposure to psychological stressors. Indeed, increases in central IL-1 production have been observed following stressors such as inescapable tailshock and social isolation, while no changes in IL-1 have been observed following other stressors (e.g., exposure to a predator). The goal of the following work was to establish whether exposure to the forced swim test (FST), a commonly used animal model of behavioral despair/depression, leads to an increase in central or peripheral production of IL-1. Briefly, adult male Sprague-Dawley rats (n=8 per group) were forced to swim for 15-30 min (25 degrees C) and killed at various intervals (ranging from immediately to 24 h) following stressor termination. Brains (hippocampus, hypothalamus, posterior cortex) and multiple peripheral tissues (pituitary, adrenals, spleen, plasma) were then dissected and frozen for subsequent measurement of IL-1 using a commercially available enzyme-linked immunosorbent assay. No observable increases in IL-1 were found in rats that were forced to swim acutely, or in rats that were re-exposed to the forced swim stressor 24 h later. These data suggest that exposure to forced swim does not lead to an increase in central production of IL-1, suggesting that the central IL-1 system is unlikely to play a role in mediating behavioral consequences of this stressor. However, these data do not exclude the possibility that other pro-inflammatory cytokines (such as IL-6 and TNF-alpha) might be produced in response to forced swim exposure.     

Antidepressant-like properties of zinc in rodent forced swim test

The effects of zinc, the N-methyl-D-aspartate glutamate receptor inhibitor, were studied in mice and rats using the forced swim test. Zinc (ZnSO4) in a dose of 30 mg/kg and imipramine (30 mg/kg), reduced the immobility time in the forced swim test in both species. Moreover, combined treatment in this test with zinc and imipramine at their ineffective doses (1 and 5 mg/kg, respectively) induced a statistically significant effect in rats. The doses active in the forced swim test reduced (in mice) or did not affect (in rats) locomotor activity. The results obtained indicate that zinc induces an antidepressant-like effect and enhances the effect of imipramine in the forced swim test, suggesting a potential antidepressant activity of zinc in humans.     

IL-6 mediated alterations on immobile behavior of rats in the forced swim test via ERK1/2 activation in specific brain regions

Interleukin-6 (IL-6), a proinflammatory cytokine, is well known as a mediator in early stage inflammatory immune reactions. In recent years, accumulating evidence has shown that IL-6 is concomitant with the occurrence of major depression. However, the identification of the role of IL-6, as either an illness causation or immunotherapy in depression, remains to be further established. In the present study, 5-week old male Sprague-Dawley (SD) rats were used along with the forced swim test (FST) and pharmacological techniques. The data show that rats subjected to 3-day intra-amygdala or intra-hippocampus, but not intra-frontal cortex, IL-6 treatments manifested a significant increase in the immobility time (IMT) in the FST. In addition, there was no obvious difference in body temperature between normal and 3-day IL-6 treated rats. Conversely, the rats receiving 3-day intra-amygdala or intra-hippocampus IL-6 inhibitor treatment expressed a significant reduction in IMT in the FST. Moreover, the 3-day IL-6 treated rats treated with SL 327, a blood-brain barrier penetrating MEK inhibitor, prior to the FST showed a significant decrease in the IL-6 elevated IMT. In addition, the results in the Western blot analysis were in parallel with those in the behavioral tests. Taken together, the results show that the immobile behavior of rats in the FST could be modulated by IL-6 via the amygdala or the hippocampus. Furthermore, the Erk1/2 activation in the amygdala or hippocampus seemed to play a role in the IL-6 mediated immobile behavioural alterations of rats in the FST.     

Antidepressant-like effects of cytidine in the forced swim test in rats.

BACKGROUND: Altered brain phospholipid metabolism may be involved in the pathophysiology of cocaine dependence and mood disorders. Evidence suggests that citicoline, a rate-limiting metabolite for phospholipid synthesis, reduces cocaine craving in human addicts. Because antidepressants can reduce cocaine craving, we explored in rats the possibility that citicoline has antidepressant effects. We also tested the primary metabolites of citicoline, cytidine and choline. METHODS: We examined if citicoline or metabolites alter immobility in the forced swim test. We used two scoring methods: latency to become immobile, a simple method that identifies antidepressants, and behavioral sampling, a complex method that differentiates antidepressants according to pharmacological mechanisms. RESULTS: Over a range of doses, citicoline did not affect behavior in the forced swim test. At molar equivalent doses, cytidine dramatically decreased immobility, whereas choline tended to increase immobility. The effects of cytidine resemble those of desipramine, a standard tricyclic antidepressant. None of the treatments affected locomotor activity, and cytidine did not establish conditioned place preferences. CONCLUSIONS: Citicoline does not have effects in the forced swim test, but its primary metabolites have opposing effects: cytidine has antidepressant-like actions, whereas choline has prodepressant-like actions. At antidepressant doses, cytidine lacks stimulant and rewarding properties. This is the first report of potential antidepressant effects of cytidine.     

Fos expression in forebrain afferents to the hypothalamic paraventricular nucleus following swim stress

The paraventricular nucleus of the hypothalamus (PVN) serves as the origin of the final common pathway in the secretion of glucocorticoid hormones in response to stress. Various stress-related inputs converge upon the cells of the medial parvocellular division of the PVN. These neurons, which synthesize and release corticotropin-releasing hormone, arginine vasopressin, and other secretagogues, are responsible for a cascade of events which culminates in the adrenocorticotropin-induced release of corticosteroids from the adrenal cortex. Previous data have suggested complex afferent regulation of PVN neurons, although the neuronal pathways by which the effects of stress are mediated remain to be fully disclosed. The present experiment sought to identify forebrain areas potentially involved in afferent regulation of the PVN in response to an acute stressor. Discrete injections of the retrograde tracer Fluoro-gold were delivered to the PVN, and rats were subsequently subjected to an acute swim stress. Brains were processed immunocytochemically for the simultaneous detection of the tracer and Fos, the protein product of the immediate early gene c-fos, utilized as a marker for neuronal activation. The majority of Fluoro-gold/Fos labeled neurons were detected in the parastrial nucleus, the medial preoptic area, the anterior hypothalamic area, the dorsomedial hypothalamic nucleus and adjacent posterior hypothalamic area, and, to a lesser extent, the supramammillary nucleus. These findings are discussed in relation to neural pathways mediating activation and inhibition of the hypothalamic-pituitary-adrenocortical axis. © 1996 Wiley-Liss, Inc.     

青霉素致(癎)大鼠海马细胞内Ca2+浓度变化与神经元单位放电的关系

目的 探讨癫(癎)大鼠海马细胞内Ca2+浓度变化和神经元单位放电的关系.方法36只Wistar雄性健康大鼠分为3组.癫(癎)模型组用青霉素钠600万U/kg腹腔注射制作成癫(癎)模型;癫(癎)预处理组在制作模型前用盐酸氟桂利嗪按20 mg/kg间隔12 h灌胃2次,第2次给药后2 h用青霉素钠600万U/kg腹腔注射制作模型.3组实验大鼠均在记录单位放电后处死,取双侧海马应用新一代钙荧光指示剂Fluo-3-AM通过流式细胞分析仪测定细胞内Ca2+荧光浓度.结果 正常对照组大鼠共记录到24个单位海马神经元放电,海马细胞内Ca2+平均荧光浓度为37.12±5.08;癫(癎)模型组共记录到78个单位海马神经元放电,海马细胞内Ca2+平均荧光浓度为52.04±6.75;癫(癎)预处理组共记录到47个单位海马神经元放电,海马细胞内Ca2+平均荧光浓度为37.79±3.09.Ca2+平均荧光值和海马单位放电个数相关系数r=0.737,P＜0.01.结论 青霉素致病大鼠海马细胞内Ca2+浓度变化与海马神经元单位放电呈正相关关系.

Abstract：

Objective To investigate the relationship between changes in Ca2+ concentration and unit discharge in the hippocampal neurons of epileptic rats.Methods Thirty-six healthy male Wistar rats were divided into three groups. Rats of the epilepsy group received an intraperitoneal injection of benzylpenicllin sodium at 6 million unit/kg; Rats of the epilepsy pretreatment group received 20 mg/kg of flunarizine at 14 and 2 hours before injection of benzylponicllin;the control group of rats received an intraperitoneal injection of normal saline.Three groups of rats were euthanized after recording of the unit discharge,and bilateral hippocampal cells were obtained to measure the cellular concentration of Ca2+ fluorescence using the new generation Ca2+ fluorescent dye Fluo-3-AM and flow cytometry.Results (1) A total of 24 units of hippocampal discharges were recorded in the control group.The average concentration Ca2+ fluorescence of the hippocampal neurons was 37.12±5.08.(2)A total of 78 units of hippocampal discharges were recorded in the epilepsy group.The average concentration of Ca2+fluorescence of the hippocampal neurons was 52.04±6.75.(3)A total of 47 units of hippocampal discharges were recorded in the epilepsy pretreatment group. The average concentration of Ca2+ fluorescence of the hippocampal neurons was 37.79±3.09.The correlation coefficient between the average concentration of Ca2+ fluorescence of the hippocampal neurons and the number of units of hippocampal discharge ( r=0.737,P＜0.01).Conclusion There is a positive correlation between changes in average concentration of Ca2+ fluorescence of the hippocampal neurons and the numbers of units of hippocampal discharge.     

The effects of perinatal anoxia or hypoxia on hippocampal kindling development in rats

The effects of anoxia and hypoxia (3% oxygen) at 10–12 post days of age on the development of ventral hippocampal kindling and its transfer to the contralateral ventral hippocampus were studied in adult male Sprague-Dawley rats. During oxygen deprivation, the heart rate decreased to 15% of the prehypoxic value in the animals exposed to anoxia and 40% in those exposed to hypoxia. As is observed in asphyxia of human newborns, our study included both ischemia and hypoxia. The susceptibility to kindling, which was measured by kindling rate, afterdischarge threshold, generalized seizure threshold, and total afterdischarge duration to stage 5, had a tendency to be enhanced in rats exposed to hypoxia compared with controls. The facilitating effects on primary site kindling were enhanced in the animals exposed to hypoxia compared with those exposed to anoxia. Transfer, which was indicated by kindling rate and afterdischarge threshold, was also slightly facilitated in the rats exposed to anoxia or hypoxia in the perinatal period. These results reveal that perinatal oxygen deficiency may not be sufficient to lead to the development of temporal lobe epilepsy. However, it is possible that perinatal hypoxia results in some pathophysiological change in the brain which leads to greater seizure susceptibility in adulthood.