ABSTRACT
Objective: To observe the influence of minocycline on expression of NF-κB, GFAP, and IL-1β in rats with vascular dementia, so as to study the neuroprotective mechanism of minocycline for vascular dementia. Methods: An animal model of vascular dementia was established by chronic bilateral common carotid artery occlusion (BCCAO). Animals were randomly divided into sham-operation group(S), 4-week model group (M4), 8-week model group (M8), 16-week model group (M16), 4-week model + Minocycline group (T4), 8-week model+Minocycline group (T8), and 16-week model+Minocycline group (T16). The behaviors of animals were tested with Morris water maze and shuttle box task. Expression of NF-κB and GFAP was measured by enzyme linked immunosorbent assay (ELISA), immunohistochemistry and Western blotting,and IL-1β by ELTSA. Results: Minocycline greatly improved the behaviors of mice with vascular dementia, and promoted the learning, memory and responding abilities. The expression of NF-κB, GFAP and IL-1β in all the model groups and Minocycline treatment groups were significantly higher than that in the sham-operation group (P<0.01); and those of Minocycline treatment groups were significantly lower than the corresponding model groups (P<0.01). Conclusion: Minocycline can decrease the expression of NF-κB, GFAP, and IL-1β in the brain of rats with vascular dementia, and protect brain by inhibiting the activation of astrocytes and neuroinflammation.
ABSTRACT
Objective: To analyze the association of recognition and behavior of diabetic rats with the expression of β-amyloid protein (Aβ) and cAMP response element binding protein (CREB), so as to pave a way for studying the role of diabetic metabolic disorder in the mechanism of Alzheimer's disease. Methods: Animal model of diabetes mellitus was established by intraperitoneal injection of streptozocin. Wistar rats were randomly divided into normal control groups (N), 4 week diabetes mellitus model group (M4), 6 week diabetes mellitus model group (M6), and 8 week diabetes mellitus model group(M8). The changes of recognition and behavior were tested by Morris water maze task and shuttle box task. Congo red staining was used to detect the deposition of beta-amyloid in the brain tissues. Expression of Aβ was measured by enzyme linked immunosorbent assay. CREB and pCREB were tested by enzyme linked immunosorbent assay, RT-PCR, and Western blotting assay. Results: Behavioral tests showed that the learning ability and memory of animals in the diabetes mellitus model groups were impaired and significantly decreased compared with those in the normal control group(P<0.01). Compared with the normal control group, the model groups showed higher Aβ expression and lower CREB and pCREB expression (P < 0.01), with no significant difference found between the three model groups. The expression of Aβ was negatively correlated with the expression of CREB and pCREB, and was positively correlated with learning and memory impairment of animals. CREB and pCREB were negatively correlated with the learning ability and memory impairment of animals. Conclusion: Diabetes mellitus can contribute to Alzheimer's disease through increasing expression of Aβ and decreasing expression of CREB and pCREB.
ABSTRACT
<p><b>OBJECTIVE</b>Nitric oxide (NO) was speculated to play an important role in the pathophysiology of cerebral ischemia. Minocycline, a tetracycline derivative, reduced inflammation and protected against cerebral ischemia. To study the neuroprotection mechanism of minocycline for vascular dementia, the influences of minocycline on expressions of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) were observed in the brains of Wistar rats.</p><p><b>METHODS</b>The vascular dementia rat model was established by permanent bilateral common carotid arteries occlusion (BCCAO). Wistar rats were divideded into 3 groups randomly: sham-operation group (S group), vascular dementia model group (M group), and minocycline treatment group (MT group). The behaviour was tested with Morris water maze and open-field task. Expressions of iNOS and eNOS were measured by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). The optical density value was measured by imaging analysis. Percentage of positive cells with iNOS and eNOS expression was analyzed with optical microscope.</p><p><b>RESULTS</b>Minocycline attenuated cognitive impairment. Inducible NOS was significantly down-regulated in MT group, compared with that in M group (P < 0.01), while eNOS was significantly up-regulated, compared with that in M group (P < 0.01). The expressions of iNOS and eNOS in M and MT groups were higher than those in S group (P < 0.01).</p><p><b>CONCLUSION</b>Minocycline can down-regulate the expression of iNOS and up-regulate the expression of eNOS in vascular dementia, which restrains apoptosis and oxidative stress to protect neural function.</p>
Subject(s)
Animals , Female , Rats , Behavior, Animal , Carotid Artery Diseases , Carotid Artery, Common , Cognition Disorders , Drug Therapy , Pathology , Disease Models, Animal , Exploratory Behavior , Hippocampus , Maze Learning , Minocycline , Therapeutic Uses , Nitric Oxide Synthase Type II , Metabolism , Nitric Oxide Synthase Type III , Metabolism , Oxidative Stress , Rats, Wistar , Reaction Time , Time FactorsABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of neural stem cell (NSC) transplantation and nerve growth factor (NGF) on neurological function recovery in rats with ischemic stroke induced by transient middle cerebral artery occlusion (MCAO).</p><p><b>METHODS</b>Cultured hippocampal NSCs isolated from neonate rats were labeled with BrdU. Sixty-four rats subjected to transient MCAO were randomized equally into 4 groups, namely group A (MCAO model group), group B (model group with NGF treatment, group C (model group with NSC transplantation), and group D (model group with both NGF and NSC transplantation). The neurological deficits of the rats were evaluated with neurological severity score (NSS) after the treatment, and the brain tissues were examined with immunohistochemical and immunofluorescent staining for BrdU and nestin expression.</p><p><b>RESULTS</b>The NSS of rats in group D 2 and 4 weeks after transplantation was significantly lower than that in the other 3 groups (P<0.05), and the scores in groups B and C were significantly lower than those in group A (P<0.05). The number of BrdU- and nestin-positive cells was significantly greater in group B than in group A (P<0.05), and BrdU-positive cells were markedly more numerous in group D than in group C (P<0.05).</p><p><b>CONCLUSION</b>Both NSC transplantation and NGF treatment can obviously improve the neurological function of rats after MCAO, but their combined use shows stronger effects. NGF can promote autologous NSC activation and proliferation, with also stimulatory effect on the proliferation of transplanted NSCs.</p>