AIMTo make approach to the relationship between the changes of free zinc and ischemic neuronal damage in hippocampus after forebrain ischemia/reperfusion.

METHODSThe models of forebrain ischemia/reperfusion were established in rats. The contents of free Zn2+ were measured by TSQ fluorescence method. The Zn2+ chelator (CaEDTA) was injected into lateral ventricles in order to evaluate the effect of free Zn2+ on ischemic neuronal damage.

RESULTS(1) Zn2+ fluorescence in the hilus of dentate gyrus, CA3 region and the stratum radiatum and stratum oriens of CA1 decreased slightly at forty-eight hours after reperfusion. From seventy-two hours to ninety-six hour after reperfusion, the decreased fluorescence gradually returned to the normal level, but some fluorescence dots were found in pyramidal neurons of CA1 and the hilus of dentate gyrus. Seven days after reperfusion, all the changes of the fluorescence almost recovered. (2) The cell membrane-impermeable Zn2+ chelator CaEDTA could reduce the intracellular concentration of free Zn2+ and reduced neuronal damage after forebrain ischemia/reperfusion.

CONCLUSION(1) The synaptic vesicle Zn2+ released and then translocated into postsynaptic neurons after forebrain ischemia/reperfusion and played a role in ischemic neuronal damage. (2) The cell membrane-impermeable chelator CaEDTA could provide neuroprotection.

Animals ; Brain Ischemia ; metabolism ; pathology ; Hippocampus ; pathology ; Male ; Neurons ; metabolism ; Rats ; Rats, Wistar ; Reperfusion Injury ; metabolism ; pathology ; Zinc ; metabolism

To explore the relationship between beta-amyloid (A beta) and the pathogenesis of Alzheimer disease (AD), after injection of beta-amyloid into the rat brain, the apoptosis of nerve cells and acetylcholine (Ach) content in rat hippocampus were examined by employing TUNEL technique and base hydroxylamine colorimetry respectively. The influence of age and glucocorticoid on the neurotoxic effect of A beta was also analyzed. A beta peptide could strongly induce the apoptosis of neurons in hippocampus, cortex and striate body (P < 0.05 or P < 0.01). In addition, the senility and glucocorticoid pre-treatment could enhance the toxic effect of A beta (P < 0.05 or P < 0.01). It is concluded that A beta may play an important role in the pathogenesis of Alzheimer disease via its induction of apoptosis of neurons and by decreasing the content of the Ach.
Acetylcholine/metabolism ; Aging ; Alzheimer Disease/etiology ; Amyloid beta-Protein/*toxicity ; Apoptosis/*drug effects ; Dexamethasone/*pharmacology ; Drug Synergism ; Hippocampus/metabolism ; Hippocampus/*pathology ; Injections, Intraventricular ; Neurons/pathology ; Rats, Wistar

OBJECTIVETo observe the effects of Huanglian Jiedu Decoction (HLJDT) on the metabolism of free radicals, the morphology and histopathology of hippocampal CA1 neurons in PS1/APP double transgenic mice of Alzheimer's disease (AD), and to study its possible mechanisms, thus providing experimental evidence for treating AD by HLJDT.

METHODSThe APP/PS1 double transgenic mouse model was used. Mice were randomly divided into five groups, i. e., the model control group, the positive control group (Aricept), high-, middle-, and low-dose HLJDT group (at the daily dose of 865 mg*kg(-1), 433 mg*kg(-1), and 216 mg*kg(-1), respectively). Corresponding medication was daily given by gastrogavage. Seven months later superoxide dismutase (SOD) and malondialdehyde (MDA) were detected at the ten-month old mice, thus observing the effects on the morphology of CA1 hippocampal neurons and the senile plaques (SP).

RESULTSHLJDT and Aricept could obviously increase the SOD contents and lower the MDA contents (P<0.05), attenuate the destroy of neurocytes and the formation of SP, effectively hinder the degeneration of hippocampal neurons. Better results were obtained in the middle-dose HLJDT group than in the positive control group (P<0.05).

CONCLUSIONThe mechanism of HLJDT in treating AD might be possibly correlated with improving anti-oxygenation, protecting hippocampal neurocytes, and reducing the formation of SP.

Alzheimer Disease ; metabolism ; pathology ; Animals ; Drugs, Chinese Herbal ; pharmacology ; Free Radicals ; metabolism ; Hippocampus ; drug effects ; pathology ; Male ; Mice ; Mice, Transgenic

Aged ; Aged, 80 and over ; Alzheimer Disease ; metabolism ; pathology ; Brain ; metabolism ; Dentate Gyrus ; metabolism ; Dynamin I ; metabolism ; Hippocampus ; metabolism ; Humans ; Monomeric Clathrin Assembly Proteins ; metabolism ; Neuropil ; metabolism ; Synaptophysin ; metabolism

The physiological functions of endogenous amyloid-β (Aβ), which plays important role in the pathology of Alzheimer's disease (AD), have not been paid enough attention. Here, we review the multiple physiological effects of Aβ, particularly in regulating synaptic transmission, and the possible mechanisms, in order to decipher the real characters of Aβ under both physiological and pathological conditions. Some worthy studies have shown that the deprivation of endogenous Aβ gives rise to synaptic dysfunction and cognitive deficiency, while the moderate elevation of this peptide enhances long term potentiation and leads to neuronal hyperexcitability. In this review, we provide a new view for understanding the role of Aβ in AD pathophysiology from the perspective of physiological meaning.
Humans ; Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Long-Term Potentiation ; Synaptic Transmission/physiology* ; Hippocampus

AIMTo evaluate N-acetylaspartate reflecting the neuronal lesion in middle cerebral artery occlusion and reperfusion rat by magnetic resonance spectroscopy (MRS).

METHODSSixteen adult Wistar rats with MCAO reperfusion and ten pseudooperation rats were performed MRS in vivo at the sixth weeks, then pathologic examination of HE staining and immunohistochemical staining were made. We compared hippocampus modality, cell density and immunohistochemical results with N-acetylaspartate, creatine changes and ration of NAA/Cr.

RESULTSThe values of NAA, Cr and NAA/Cr of ipsilateral hippocampus lesion in MCAO reperfusion rats (2.05 +/- 0.33, 2.42 +/- 0.41 and 0.86 +/- 0.10) were visiblly decreased than contralateral hippocampus (3.45 +/- 0.58, 3.10 +/- 0.93, 1.18 +/- 0.32) and control group (3.42 +/- 0.43, 3.57 +/- 0.47, 0.98 +/- 0.14). But the level of decreased NAA is not corresponding to the degree of neuronal death in ipsilateral region of hippocampus in histochemistry.

CONCLUSIONMRS has perfect explanation of cell metabolic changes in CA1 region. Decrease of NAA represented neuron delayed injury. But the decreased level of NAA is not perfectly corresponded to the degree of neuron lost. This change has closed correlation with reactive astrocytes proliferation.

Animals ; Aspartic Acid ; analogs & derivatives ; metabolism ; Brain Ischemia ; metabolism ; pathology ; Female ; Hippocampus ; cytology ; pathology ; Magnetic Resonance Spectroscopy ; methods ; Male ; Neurons ; metabolism ; pathology ; Rats ; Rats, Wistar

Amyloid beta (Aβ) plaques are one of the hallmarks of Alzheimer's disease (AD). However, currently available anti-amyloid therapies fail to show effectiveness in the treatment of AD in humans. It has been found that there are different types of Aβ plaque (diffuse and focal types) in the postmortem human brain. In this study, we aimed to investigate the correlations among different types of Aβ plaque and AD-related neuropathological and cognitive changes based on a postmortem human brain bank in China. The results indicated that focal plaques, but not diffuse plaques, significantly increased with age in the human hippocampus. We also found that the number of focal plaques was positively correlated with the severity of AD-related neuropathological changes (measured by the "ABC" scoring system) and cognitive decline (measured by the Everyday Cognitive Insider Questionnaire). Furthermore, most of the focal plaques were co-localized with neuritic plaques (identified by Bielschowsky silver staining) and accompanied by microglial and other inflammatory cells. Our findings suggest the potential of using focal-type but not general Aβ plaques as biomarkers for the neuropathological evaluation of AD.
Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Amyloid beta-Protein Precursor ; Brain/pathology* ; Cognitive Dysfunction/pathology* ; Hippocampus/metabolism* ; Humans ; Neuroinflammatory Diseases ; Plaque, Amyloid/pathology*

OBJECTIVETo investigate whether there is endogenous neural stem cell proliferation and whether these proliferated neural stem cells represent neural plasticity in the adult rats after cerebral infarction.

METHODSCerebral infarction models of rats were established and the dynamic expression of bromodeoxyuridine (BrdU), BrdU/polysialylated neural cell adhesion molecule (PSA-NCAM) were determined by immunohistochemistry and immunofluorescence staining. BrdU was used to mark dividing neural stem cells. PSA-NCAM was used to mark the plasticity of neural stem cells.

RESULTSCompared with controls, the number of BrdU-positive cells in the subventricular zone (SVZ) and hippocampus increased significantly at 1st day after cerebral infarction (P < 0.05), reached maximum at 7th day, decreased markedly at 14th day, but it was still elevated compared with that of the controls (P < 0.05). The number of BrdU-labeled with PSA-NCAM-positive cells increased significantly at 7th day (P < 0.05), reached maximum at 14th day, markedly decreased at 28th day, but it was still elevated compared with that of the controls (P < 0.05). It was equal to 60% of the number of BrdU-positive cells in the same period.

CONCLUSIONCerebral infarction may stimulate the proliferation of endogenous neural stem cells in situ and most proliferated neural stem cells represent neural plasticity.

Animals ; Bromodeoxyuridine ; metabolism ; Cell Proliferation ; Cerebral Infarction ; metabolism ; pathology ; Cerebral Ventricles ; pathology ; Hippocampus ; pathology ; Male ; Neural Cell Adhesion Molecule L1 ; metabolism ; Neuronal Plasticity ; Neurons ; metabolism ; pathology ; Rats ; Rats, Wistar ; Sialic Acids ; metabolism ; Stem Cells ; metabolism ; pathology

OBJECTIVETo investigate effect of chronic transauricular kindled seizures on passive-avoidance test memory retention in rats.

METHODSChronic transauricular kindled seizures was induced by repeated application of initially subconvulsive electrical stimulation through ear-clip electrodes once every 24 h until the occurrence of 3 consecutive clonic-tonic seizures. A passive avoidance test was used to measure memory retention ability. Morphological changes in neurons of hippocampal CA1 region was examined after HE staining. Histamine, gamma-aminobutyric acid (GABA) and glutamate levels in the hippocampus were measured by high performance liquid chromatography (HPLC).

RESULTChronic transauricular kindled seizures impaired passive-avoidance test memory retention in rats. The damaged CA1 neurons were observed and histamine content in the hippocampus markedly decreased 24 h after the end of kindling in the chronic transauricular kindled rats.

CONCLUSIONChronic transauricular kindled seizure impaired passive-avoidance test memory retention, and it might be due to the damaged CA1 neurons and a decrease of histamine in the hippocampus induced by epilepsy.

Animals ; Avoidance Learning ; Hippocampus ; metabolism ; pathology ; physiopathology ; Histamine ; metabolism ; Kindling, Neurologic ; Male ; Memory Disorders ; etiology ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Seizures ; metabolism ; pathology ; physiopathology ; gamma-Aminobutyric Acid ; metabolism

OBJECTIVETo observe the effects of hyperbaric oxygen (HBO) on synaptic ultrastructure and the synaptophysin expression (p38) in hippocampal CA3 after hypoxia-ischemic brain damage (HIBD) in neonatal rats.

METHODSThe rat model of HIBD was made by the method of Bjelke and divided randomly into two groups (n = 10)--HIBD group and HBO-treated HIBD group. Another 20 rats underwent sham-operation and were also divided randomly into HBO-treated control group and the control group. After 24 h of the operation, the rats of the HBO-treated groups received HBO (2ATA, 1 h/d) for 14 days. When rats were 4 weeks old, the learning-memory ability of rats in every group was evaluated through water-maze test. Their hippocampal ultrastructure was observed with electron microscope and the p38 expression was detected immunohistochemically.

RESULTSCompared with the control group [(10.6 +/- 3.4) times], the water-maze learning ability of the rats in HIBD group [(15.5 +/- 4.9) times] was significantly decreased (P < 0.01), while the learning-memory ability of the HBO-treated HIBD group [(11.3 +/- 2.6) times] was significantly improved. There was no significant difference in the water-maze test between the HBO-treated HIBD group and the control group (P > 0.05). Compared with the control group, the ultrastructure of pyramidal neuron of hippocampal CA3 was distorted in HIBD group under the electron microscope. Compared with that in HBO-treated HIBD group (0.77 +/- 0.17, 0.67 +/- 0.16, 0.46 +/- 0.13, 0.86 +/- 0.14) and the control group (0.82 +/- 0.16, 0.70 +/- 0.16, 0.53 +/- 0.15, 0.91 +/- 0.17), the corrected optical densities (COD) of immunoreactive products of the hippocampal CA3 p38 were significantly decreased in HIBD group (0.41 +/- 0.19, 0.21 +/- 0.11, 0.08 +/- 0.03, 0.38 +/- 0.16) (P < 0.01). There was no significant difference in either ultrastructure or immunohistochemically reactive COD of p38 between the HBO-treated HIBD group and the control group (P > 0.05).

CONCLUSIONUnderlying the induction of synaptic plasticity and reducing the ultrastructural damage may be involved in the mechanism of HBO in the brain rehabilitation in perinatal brain damage with hypoxia-ischemia.

Animals ; Animals, Newborn ; Female ; Hippocampus ; metabolism ; pathology ; Hyperbaric Oxygenation ; Hypoxia-Ischemia, Brain ; metabolism ; pathology ; therapy ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Synapses ; metabolism ; ultrastructure ; Synaptophysin ; metabolism