Neuroprotective effects of resveratrol against traumatic brain injury in immature rats

Childhood trauma resulting in traumatic brain injury (TBI) due to accidents and abuse is the major cause of death and dysfunction in the young. Since there are no approved specific pharmacological agents that block the progression of the secondary injury, the current management of TBI is mainly supportive. We aimed to determine the effect of resveratrol on hippocampal damage and behavioral deficits in 7-day-old rat pups subjected to contusion injury. Resveratrol was injected intraperitoneally at the doses of 100 mg/kg of body weight immediately after induction of traumatic injury. Hippocampal damage was examined by cresyl violet staining and behavioral alterations were evaluated using open field and novel object recognition tests 2 weeks after trauma. Histopathological evaluation showed that treatment with a single dose of 100 mg/kg resveratrol (i.p.) after the trauma significantly ameliorated the trauma induced hippocampal neuron loss at ipsilateral and contralateral hippocampal brain regions of rats. Additionally, treatment with resveratrol decreased anxiety and increased cortex/hippocampus dependent memory of animals subjected to blunt head trauma. These results show that acute treatment of resveratrol has a neuroprotective role against trauma induced hippocampal neuron loss and associated cognitive impairment in rats.     

The selective 5-HT(1A) receptor agonist repinotan HCl attenuates histopathology and spatial learning deficits following traumatic brain injury in rats

The selective 5-HT(1A) receptor agonist Repinotan HCl (BAY x3702) has been reported to attenuate cortical damage and improve functional performance in experimental models of cerebral ischemia and acute subdural hematoma. Using a clinically relevant contusion model of traumatic brain injury, we tested the hypothesis that a 4-h continuous infusion of Repinotan HCl (10 microg/kg/h i.v.) commencing 5 min post-injury would ameliorate functional outcome and attenuate histopathology. Forty isoflurane-anesthetized male adult rats were randomly assigned to receive either a controlled cortical impact (2.7 mm tissue deformation, 4 m/s) or sham injury (Injury/Vehicle=10, Injury/MK-801=10, Injury/Repinotan HCl=10, Sham/Vehicle=10), then tested for vestibulomotor function on post-operative days 1-5 and for spatial learning on days 14-18. Neither Repinotan HCl nor the non-competitive N-methyl-D-aspartate receptor antagonist MK-801, which served as a positive control, improved vestibulomotor function on beam balance and beam walk tasks relative to the Injury/Vehicle group, but both did significantly attenuate spatial learning and memory deficits on a water maze task. Repinotan HCl also reduced hippocampal CA(1) and CA(3) neuronal loss, as well as cortical tissue damage, compared to the Injury/Vehicle group at 4 weeks post-trauma. No significant difference in histological outcome was revealed between the Repinotan HCl- and MK-801-treated groups.These findings extend the therapeutic efficacy of Repinotan HCl to a contusion model of experimental brain injury and demonstrate for the first time that 5-HT(1A) receptor agonists confer neuroprotection and attenuate spatial learning deficits following controlled cortical impact injury. This treatment strategy may be beneficial in a clinical context where memory impairments are common following human traumatic brain injury.     

Relationship between circulating IGF-1 levels and traumatic brain injury-induced hippocampal damage and cognitive dysfunction in immature rats

It is well known that traumatic brain injury (TBI) induces the cognitive dysfunction resulting from hippocampal damage. In the present study, we aimed to assess whether the circulating IGF-I levels are associated with cognition and hippocampal damage in 7-day-old rat pups subjected to contusion injury. Hippocampal damage was examined by cresyl violet staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Spatial memory performance was assessed in the Morris water maze. Serum IGF-1 levels decreased in both early and late period of TBI. Decreased levels of serum IGF-1 were correlated with hippocampal neuron loss and spatial memory deficits. Circulating IGF-1 levels may be predictive of cognitive dysfunction resulted from hippocampal damage following traumatic injury in developing brain. Therapy strategies that increase circulating IGF-1 may be highly promising for preventing the unfavorable outcomes of traumatic damage in young children.     

低剂量木黄酮降低缺血后神经元损伤并改善学习记忆功能

目的探讨染料木黄酮(GEN)对全脑缺血(GCI)大鼠海马CA1区神经元的神经保护作用及其可能的机制。方法建立大鼠4动脉结扎全脑缺血模型,实验动物随机分为假手术组(sham)、缺血再灌注组(I/R)、GEN处理组、ICI 182,780组和溶剂对照组。采用Fluoro-Jade B和神经元特异性核蛋白(NeuN)染色观察海马CA1区神经元存活情况,TUNEL技术观察海马CA1区神经元的凋亡。Morris水迷宫观察大鼠的空间学习和记忆功能。结果 GEN发挥神经保护作用的最佳剂量为1.0 mg/kg;与sham组相比,I/R组和溶剂对照组海马CA1区TUNEL阳性神经元数量显著增多(P0.01),而1.0 mg/kg GEN可显著降低缺血后TUNEL阳性神经元数量(P0.01);与I/R组相比,GEN能明显改善缺血后大鼠的空间学习和记忆能力。缺血前侧脑室给予ICI 182,780可显著降低GEN的神经保护作用(P0.01)。结论低剂量(1.0mg/kg)GEN可显著降低缺血后大鼠海马CA1区神经元损伤,改善认知功能,其分子机制可能与雌激素受体活性密切相关。     

Neuroprotection and functional recovery conferred by administration of kappa- and delta 1-opioid agonists in a rat model of global ischemia

Studies that have evaluated the beneficial effect of pre-ischemic treatment of kappa-opioid receptor agonists have used short-term reperfusion intervals. We examined the long-term impact of the pre-ischemic peripheral injection of U50,488H (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide), a selective kappa-opioid receptor agonist, on neuronal damage and behavioral deficits following global ischemia in rats. Four groups of ischemic rats were pretreated with various doses of U50,488H (i.p. 0, 5, 15, 30 mg/kg) 15 min prior to vessel occlusion. Two groups of sham-operated animals that received either saline or U50,488H (30 mg/kg) acted as controls. The injection of 30 mg/kg U50,488H led to a 65% increase in CA1 neuron survival 35 days post-ischemia. CA1 neuronal protection translated into significant improvement of ischemia-induced spatial memory deficits assessed in the 8-arm radial maze. However, there was no difference in activity in the open field. We also found that the pre-ischemic intracerebroventricular injection of 5 mug of the delta1-opioid receptor agonist DPDPE ([d-Pen(2,5)]-enkephalin) produced a 59% increase in CA1 neuron survival 7 days post-ischemia. Similar to U50,488H, DPDPE had no significant impact on locomotor activity. These findings support a role for kappa- and delta-opioid receptors in attenuation of ischemia-induced hippocampal damage and cognitive impairments.     

Tetrahydroaminoacridine alleviates medial septal lesion-induced and age-related spatial reference but not working memory deficits

This study examined the effects of tetrahydroaminoacridine (THA, an anticholinesterase) on water-maze (WM) spatial reference (stable platform location during training) and spatial working memory (reversal of platform location) learning in young intact/medial septal (MS)-lesioned and aged rats. THA (1 or 3 mg/kg, IP) had no effect on reference or working memory performance of young intact rats. MS lesions decreased cholineacetyltransferase activity in the hippocampus and also impaired spatial reference and working memory. THA at 3 mg/kg stabilized MS lesion-induced reference memory performance deficit (path length increase), but was ineffective at 1 mg/kg. THA had no effect on the working memory performance of MS-lesioned rats. Aged rats were impaired in spatial reference and working memory tasks. THA at 3 mg/kg partially stabilized the age-induced spatial reference memory deficits, but was ineffective at 1 mg/kg. THA at either 1 or 3 mg/kg did not alleviate the age-related deficit in the working memory version of WM. The present results suggest that some of the age-related WM deficits may be related to the degeneration of the MS-hippocampus cholinergic system and that THA may be effective in stabilizing the reference memory deficits induced by hippocampal cholinergic dysfunction.     

Follicular dynamic and immunoreactions of the vitrified ovarian graft after host treatment with variable regimens of melatonin

Citation
Hemadi M, Shokri S, Pourmatroud E, Moramezi F, Khodadai A. Follicular dynamic and immunoreactions of the vitrified ovarian graft after host treatment with variable regimens of melatonin. Am J Reprod Immunol 2012; 67: 401–412 Problem This study investigates dose‐dependent effects of melatonin on ovarian graft. Method of Study Vitrified‐thawed whole ovaries of newborn mice were grafted into ovariectomized mature ones. Melatonin (20, 50, 100, and 200 mg/kg/day) was administrated to separate groups of host mice for 32 days. IgM and IgG antibodies, Th1 and Th2 cytokines, and melatonin in recipient’s blood were measured. Subsequent survival of the grafted ovaries was scored. An assessment of follicular morphology was performed using TUNEL assay and hematoxylin‐eosin staining. Results The administration of melatonin did not disturb the circadian rhythm of melatonin concentration. The ovarian graft lifespan was prolonged at 200 mg/kg/day melatonin (P < 0.001). However, in doses of higher than 20 mg/kg/day melatonin, the proportion of healthy follicles and ovary size decreased. Th1 cytokines levels were reduced dose dependently. However, the effect of melatonin on Th2 cytokines was not pronounced. IgM and IgG2a decreased in recipients receiving 200 mg/kg/day melatonin in comparison with non‐treated group (P < 0.001), while this variables were significantly increased at the dose of 50 mg/kg/day (P < 0.001). Conclusion Melatonin at 200 mg/kg/day has an immunosuppresent effect and produce prolongation of graft survival. However, the associated reduction in healthy follicles suggests that melatonin in doses of higher than 20 mg/kg/day has no preventative ischemic action.     

Dexamethasone induces limited apoptosis and extensive sublethal damage to specific subregions of the striatum and hippocampus: implications for mood disorders

It has been shown previously that the synthetic corticosteroid dexamethasone induces apoptosis of granule cells in the dentate gyrus and striatopallidal neurons in the dorsomedial caudate-putamen. We investigated whether or not dexamethasone can induce damage to other neuronal populations. This issue was addressed using OX42 immunohistochemistry to visualise activated microglia and thereby gauge the extent of dexamethasone-induced neuronal death. A single dose of dexamethasone (20mg/kg, i.p.) administered to young male Sprague-Dawley rats induced a strong microglial reaction which was restricted to the striatum, the dentate gyrus and all of the CA subfields of the hippocampus. Some OX42-immunoreactive cells were also seen in the lateral septal nucleus. Subsequent quantitative analysis of silver/methenamine-stained sections confirmed that acute administration of dexamethasone induced apoptosis in the striatum and all regions of the hippocampus at doses as low as 0.7mg/kg. In contrast, dexamethasone failed to induce apoptosis in the lateral septal nucleus at doses up to 20mg/kg. The levels of dexamethasone-induced striatal and hippocampal apoptosis were attenuated by pretreatment with the corticosteroid receptor antagonist RU38486 (Mifepristone), which implies that the cell death was mediated by a corticosteroid receptor-dependent process. We further determined whether dexamethasone induced sublethal damage to neurons by quantifying reductions in the number of microtubule-associated protein-2-immunoreactive striatal and hippocampal cells following injection of the corticosteroid. Dexamethasone induced dramatic decreases in the striatum, with the dorsomedial caudate-putamen being particularly affected. Similar damage was seen in the hippocampus, with the dentate gyrus and CA1 and CA3 subfields being particularly vulnerable.Equivalent corticosteroid-induced neuronal damage may occur in mood disorders, where the levels of endogenous corticosteroids are often raised. Corticosteroid-induced damage of striatal and hippocampal neurons may also account for some of the cognitive deficits seen following administration of the drugs to healthy volunteers.     

Two phases of behavioral plasticity in rats following unilateral excitotoxic lesion of the hippocampus.

We investigated the effects of dizocilpine, a non-competitive N-methyl-D-aspartate receptor antagonist, on spatial reference and working memory in a radial arm maze task in rats with a unilateral hippocampal lesion. At a dose of 0.2 mg/kg to intact rats, dizocilpine significantly impaired both reference and working memory, and produced ataxia and impairment of food intake; at 0.1 mg/kg, dizocilpine had no effect on performance. Unilateral hippocampal lesion induced by quinolinic acid produced a marked working memory deficit concomitant with a slight but significant impairment of reference memory when mnemonic ability was examined one week after the lesion. The spatial memory deficits in the rats with a unilateral hippocampal lesion were ameliorated by repeated daily trainings over a 21-day period. Following recovery of the spatial memory deficits produced by the brain lesion (four weeks after the brain lesion), dizocilpine (0.1 mg/kg) significantly impaired both reference and working memory, without affecting general behavior or food intake in the brain-lesioned rats. An impairment of working memory, but not reference memory, by dizocilpine was observed six weeks after the brain lesion. However, the disrupting effect of dizocilpine at 0.1 mg/kg on spatial working memory had disappeared at eight weeks after the lesion. Ten weeks after the brain lesion, dizocilpine at 0.2 mg/kg was necessary to induce spatial memory impairment, which was accompanied by motor and food intake deficits, as in intact rats. In sham-operated rats, the dose-response effects of dizocilpine did not differ from those in intact rats at any time after the operation. These results suggest that two phases of behavioral plasticity take place, depending on demand, to compensate for brain dysfunction after the unilateral lesion of the hippocampus in rats.     

Dual effects of melatonin on barbiturate-induced narcosis in rats

Melatonin affects the circadian sleep/wake cycle, but it is not clear whether it may influence drug-induced narcosis. Sodium thiopenthal was administered intraperitoneally into male rats pre-treated with melatonin (0.05, 0.5, 5 and 50 mg/kg). Melatonin pre-treatment affected in a dual manner barbiturate narcosis, however, no dose-effect correlation was found. In particular, low doses reduced the latency to and prolonged the duration of barbiturate narcosis. In contrast, the highest dose of melatonin (50 mg/kg) caused a paradoxical increase in the latency and produced a sustained reduction of the duration of narcosis, and a reduction in mortality rate. Melatonin 0.5 and 5 mg/kg influenced the duration but not the latency of ketamine- or diazepam-induced narcosis. Thus, the dual action of melatonin on pharmacological narcosis seems to be specific for the barbiturate mechanism of action.     

Impaired SynGAP expression and long-term spatial learning and memory in hippocampal CA1 area from rats previously exposed to perinatal hypoxia-induced insults: beneficial effects of A68930

Hypoxic encephalopathy is a common cause of neonatal seizures and long-term neurological cognitive deficits. In rats at postnatal days 10-12 (P10-P12), global hypoxia induced spontaneous seizures and chronic brain injury, mimicking clinical aspects of neonatal hypoxia. Synaptic Ras-GTPase activating protein (SynGAP) has important roles in RAS/MAPK-dependent synaptic plasticity and mammalian learning. We investigated possible alterations of SynGAP expression occurring in memory-impaired animals previously exposed to perinatal hypoxia insults. We also evaluated the therapeutic efficacy of A68930, a selective agonist of dopamine D1/D5 receptors, on perinatal hypoxia insults. In the hippocampal CA1 region, perinatal hypoxia insults (P10) led to a reduction in SynGAP expression associated with impairment in long-term spatial learning and memory performance at P45. The use of A68930 (at a dose of 1, 2, 3mg/kg, P17-P23) effectively attenuated the deleterious effects as described above. Our results may indicate the involvement of SynGAP in certain forms of brain injury, leading to long-term learning and memory deficits. A68930 may have clinical potential as a therapeutic agent for alleviation of long-term cognitive deficits in rats and other animal models.     

白藜芦醇对花萼海绵诱癌素所致小鼠空间记忆障碍的预防作用

目的:探讨腹腔注射白藜芦醇对昆明小鼠侧脑室注射花萼海绵诱癌素引起的空间记忆障是否有预防作用。方法:2月龄昆明小鼠44只随机分为4组,分别为生理盐水对照组、模型组、白藜芦醇低剂量组和白藜芦醇高剂量组;生理盐水对照组和模型组腹腔注射等体积生理盐水,白藜芦醇低剂量组和白藜芦醇高剂量组分别腹腔注射白藜芦醇5 mg/kg和10 mg/kg共21 d,除对照组外,第22天从侧脑室注射花萼海绵诱癌素4μL,第27天进行Morris水迷宫定位航行训练,持续6 d,24 h后进行寻找平台潜伏期检测。再处死小鼠,进行灌流固定做高尔基染色观察神经元树突和树突棘,并取新鲜脑海马匀浆后检测SOD活性。结果:白藜芦醇低剂量组显著缩短侧脑室注射花萼海绵诱癌素引起的逃避潜伏期。白藜芦醇低剂量组显著增加侧脑室注射花萼海绵诱癌素引起的CA1区锥体神经元树突的长度和分枝数目。白藜芦醇低剂量组显著增加侧脑室注射花萼海绵诱癌素引起的海马CA1区锥体神经元树突棘的密度。白藜芦醇高剂量组显著增加花萼海绵诱癌素引起的海马SOD活性,而低剂量组并不改变SOD活性。结论:低剂量白藜芦醇对侧脑室注射花萼海绵诱癌素引起的空间记忆障碍具有预防作用,其机制可能与减轻花萼海绵诱癌素引起的树突损伤有关。     

褪黑素对阿尔茨海默病模型大鼠学习记忆能力及海马CA3区神经元的保护作用

目的 观察褪黑素(MT)对阿尔茨海默病(AD)模型大鼠学习记忆及海马CA3区神经元的保护作用.方法 随机将60只雄性Wistar大鼠分为正常对照组、AD模型组与MT治疗组.采用右侧海马CA1区注射β-淀粉样蛋白1～40(Aβ1～40)构建AD动物模型,MT治疗组以MT(10mg/kg·d)腹腔注射,正常对照组与AD模型...     

Neuroprotective effect of ginseng total saponins in experimental traumatic brain injury

In the present study, we investigated whether ginseng total saponins (GTSs) protect hippocampal neurons after experimental traumatic brain injury (TBI) in rats. A moderate-grade TBI was made with the aid of a controlled cortical impact (CCI) device set at a velocity of 3.0 m/sec, a deformation of 3.0 mm, and a compression time of 0.2 sec at the right parietal area for adult male Sprague-Dawley rats. Shamoperated rats that underwent craniectomy without impact served as controls. GTSs (100 and 200 mg/kg) or saline was injected intraperitoneally into the rats immediately post-injury. Twenty-four hours after the injury, the rats underwent neurological evaluation. Contusion volume and the number of hippocampal neurons were calculated with apoptosis evaluated by TUNEL staining. 24 hr post-injury, saline-injected rats showed a significant loss of neuronal cells in the CA2 region of the right hippocampus (53.4%, p<0.05) and CA3 (34.6%, p<0.05) compared with contralateral hippocampal region, a significant increase in contusion volume (34+/-8 microL), and significant increase in neurologic deficits compared with the GTSs groups. Treating rats with GTSs seemed to protect the CCI-induced neuronal loss in the hippocampus, decrease cortical contusion volume, and improve neurological deficits.     

Influence of dizocilpine (MK-801) on neurotoxic effect of dexamethasone: behavioral and histological studies

Elevated levels of endogenous glucocorticoids (GCs) or prolonged treatment with high doses of dexamethasone (DEX) or other GCs preparations are frequently associated with psychosis as well as cognitive deficits, such as the impairment of memory and learning. GCs potentiate stress or ischemia-induced accumulation of excitatory amino acids in the extracellular space of hippocampus. The antagonism of glutamate receptors may potentially improve safety profile of therapy with GCs. The purpose of the present study was to investigate the effect of dizocilpine maleate (MK-801), non-competitive NMDA glutamate receptor antagonist, on neurotoxic effect of the prolonged treatment with the high dose of DEX. The results showed that DEX (120 mg/kg/day for 7 days) impaired the long-term memory and the motor coordination, reduced the body weight and induced the lethality of mice. The morphological and ultrastructural study have confirmed damage to hippocampal neurons especially in the CA3 region after the prolonged treatment with DEX alone. Damaged pyramidal neurons showed robust changes in the shape of the nucleus and cytoplasm condensation. MK-801 alone (at non-toxic dose of 0.3 mg/kg/day), changed neither the behavior of mice nor morphology of the hippocampal neurons. However, it did not prevent the neurotoxic effects of DEX. On the contrary, it intensified DEX-induced neurotoxicity.     

二苯乙烯苷对沙鼠脑缺血/再灌注引发海马损伤的保护作用

目的　研究二苯乙烯苷（tetrahydroxy stilbene glucoside, TSG）对脑缺血/再灌注（ischemia/reperfusion, I/R）沙鼠脑海马损伤的保护作用及可能机制。 方法 采用结扎沙鼠双侧颈动脉缺血30 min,再灌注5 d复制沙鼠全脑I/R模型。沙鼠随机分为6组,假手术组、模型对照组、TSG大、中、小剂量（6、3、1.5 mg/kg）组和阳性对照药依达拉奉注射组（3 mg/kg）。5 d后通过Morris水迷宫测定沙鼠学习记忆功能;Nissl染色观察沙鼠大脑海马CA1区神经元结构和数量的变化;TUNEL染色法观察沙鼠大脑海马CA1区神经元凋亡的变化;Western blot法检测脑组织active-caspase-3的表达。 结果　与假手术组相比,I/R组沙鼠学习记忆能力明显降低,海马CA1区神经元大量丢失,结构紊乱。同时,I/R组沙鼠CA1区神经元凋亡数量明显增加,脑组织中caspase-3显著活化。TSG中、高（3、6 mg/kg）剂量组和依达拉奉阳性对照组均可以显著改善I/R引发的沙鼠学习记忆能力的降低,抑制海马CA1区神经元的丢失,改善神经元结构;抑制CA1区神经元的凋亡以及caspase-3的活化。而TSG低剂量组对上述变化均没有明显的治疗作用。 结论　TSG对于I/R引发的脑损伤,尤其是海马区神经元迟发性凋亡具有明显的治疗作用,这种作用与其抑制caspase-3的活化相关。     

Vitamin D receptor gene polymorphism and its association with Parkinson's disease in Chinese Han population

Decreased cerebral blood flow causes cognitive impairments and neuronal injury in vascular dementia. In the present study, we reported that donepezil, a cholinesterase inhibitor, improved transient global cerebral ischemia-induced spatial memory impairment in gerbils. Treatment with 5 mg/kg of donepezil for 21 consecutive days following a 10-min period of ischemia significantly inhibited delayed neuronal death in the hippocampal CA1 region. In Morris water maze test, memory impairment was significantly improved by donepezil treatment. Western blot analysis showed that donepezil treatment prevented reductions in p-CaMKII and p-CREB protein levels in the hippocampus. These results suggest that donepezil attenuates the memory deficit induced by transient global cerebral ischemia and this neuroprotection may be associated with the phosphorylation of CaMKII and CERB in the hippocampus.     

Pinealectomy causes hippocampal CA1 and CA3 cell loss: reversal by melatonin supplementation

This experiment determined if the loss of endogenous melatonin via pinealectomy affected rat CA1 and CA3 pyramidal neuron numbers over a 20-month span. Since pinealectomy eliminates many neurohormones, some rats received daily melatonin supplementation to determine if this would reverse its effects. CA1 pyramidal cells were significantly reduced between 2 and 4 months after pinealectomy. CA3 loss was evident at 2 months post-pinealectomy. Melatonin replacement in the drinking water prevented these effects and seemingly promoted the genesis of CA1 cells. Analyses of hippocampal thiobarbituric acid reactive substances (TBARS) levels at 3 and 20 months post-surgery, revealed no significant group differences in lipid peroxidation. However, hippocampal TBARS were higher at 20 than at 3 months in all groups. Pinealectomized rats exhibited a significantly higher ratio of reduced to oxidized glutathione at 3 months but not 20 months, when compared to the sham and melatonin-supplemented rats. This suggests that pinealectomy caused oxidative stress and a subsequent compensatory change in the glutathione system. These results indicate that endogenous melatonin is neuroprotective.     

Long-term study of dendritic spines from hippocampal CA1 pyramidal cells, after neuroprotective melatonin treatment following global cerebral ischemia in rats

Melatonin reduces pyramidal neuronal death in the hippocampus and prevents the impairment of place learning and memory in the Morris water maze, otherwise occurring following global cerebral ischemia. The cytoarchitectonic characteristics of the hippocampal CA1 remaining pyramidal neurons in brains of rats submitted 120 days earlier to acute global cerebral ischemia (15-min four vessel occlusion, and melatonin 10mg/(kg h 6h), i.v. or vehicle administration) were compared to those of intact control rats in order to gain information concerning the neural substrate underlying preservation of hippocampal functioning. Hippocampi were processed according to a modification of the Golgi method. Dendritic bifurcations from pyramidal neurons in both the oriens-alveus and the striatum radiatum; as well as spine density and proportions of thin, stubby, mushroom-shaped, wide, ramified, and double spines in a 50 microm length segment of an oblique dendrite branching from the apical dendrite of the hippocampal CA1 remaining pyramidal neurons were evaluated. No impregnated CA1 pyramidal neurons were found in the ischemic-vehicle-treated rats. CA1 pyramidal neurons from ischemic-melatonin-treated rats showed stick-like and less ramified dendrites than those seen in intact control neurons. In addition, lesser density of spines, lower proportional density of thin spines, and higher proportional density of mushroom spines were counted in ischemic-melatonin-treated animals than those in the sinuously branched dendrites of the intact control group. These cytoarchitectural arrangements seem to be compatible with place learning and memory functions long after ischemia and melatonin neuroprotection.     

Morphologic and behavioral effects of perinatal glucocorticoid administration

Male rats were infused with one of two doses of dexamethasone or saline on day 4 of life. Body, whole brain, hippocampal, and cerebellar weights were obtained at 10, 20 and 150 days of age, and the ability of the rats to acquire and reverse a spatial discrimination task was assessed at 90 days of age. Body weights and brain weights were severely and permanently suppressed in the high dose group (100 mg/kg), resulting in a 20% decrement from saline-injected controls in adulthood. Low dose (1 mg/kg) animals were transiently slowed in body and brain growth, but differences from controls were no longer detectable at 60 days of age. Both high dose and low dose animals were significantly impaired in acquisition and reversal of a spatial learning task in an open field water maze, and exhibited deficits characteristically seen in animals with hippocampal damage. The animals' swimming performance per se was unimpaired. It appears that even transient interruption of normal interactive sequences of brain development by the alteration of post-natal neurogenesis or gliogenesis by glucocorticoids results in a permanent behavioral deficit.