Recombinant human erythropoietin upregulates PPARγ through the PI3K/Akt pathway to protect neurons in rats subjected to oxidative stress.

In vitro cell experiments have suggested that recombinant human erythropoietin (rhEPO) and peroxisome proliferator activated receptor γ (PPARγ) activation exert protective effects on neurons. This study observed the learning and memory ability, antioxidant capacity and the ratio of apoptotic cells after rhEPO intervention and investigated the relationship among rhEPO, PI3K/Akt and PPARγ in the anti-neural oxidative stress injury process in vivo. The results showed that rhEPO significantly improved the learning and memory abilities of rats subjected to oxidative stress, enhanced the antioxidant capacity of cells, and reduced neuronal apoptosis. Then, the PI3K/Akt and PPARγ pathways were inhibited, and TUNEL staining were used to observe the changes in the effect of rhEPO. After the PI3K/Akt and PPARγ pathways were inhibited, the effect of rhEPO on rats subjected to oxidative stress was significantly weakened, suggesting that both the PI3K/Akt and PPARγ pathways are involved in the process by which rhEPO protects neurons. Finally, Western blotting and immunofluorescence staining were used to observe the changes in PI3K/Akt and PPARγ signalling proteins in the neurons after the rhEPO intervention and to explore the relationship among the three. The results showed that rhEPO significantly increased the levels of the p-Akt and PPARγ proteins and the level of the PPARγ protein in the nucleus, indicating that the PI3K/Akt pathway was located upstream of and regulates PPARγ. In conclusion, this study suggested that rhEPO activates the PI3K/Akt to upregulate PPARγ, enhance the cellular antioxidant capacity, and protect neurons in rats subjected to oxidative stress.

Inhibiting HMGB1-RAGE axis prevents pro-inflammatory macrophages/microglia polarization and affords neuroprotection after spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) favors a persistent pro-inflammatory macrophages/microglia-mediated response with only a transient appearance of anti-inflammatory phenotype of immune cells. However, the mechanisms controlling this special sterile inflammation after SCI are still not fully elucidated. It is known that damage-associated molecular patterns (DAMPs) released from necrotic cells after injury can trigger severe inflammation. High mobility group box 1(HMGB1), a ubiquitously expressed DNA binding protein, is an identified DAMP, and our previous study demonstrated that reactive astrocytes could undergo necroptosis and release HMGB1 after SCI in mice. The present study aimed to explore the effects and the possible mechanism of HMGB1on macrophages/microglia polarization, as well as the neuroprotective effects by HMGB1 inhibition after SCI. METHODS: In this study, the expression and the concentration of HMGB1 was determined by qRT-PCR, ELISA, and immunohistochemistry. Glycyrrhizin was applied to inhibit HMGB1, while FPS-ZM1 to suppress receptor for advanced glycation end products (RAGE). The polarization of macrophages/microglia in vitro and in vivo was detected by qRT-PCR, immunostaining, and western blot. The lesion area was detected by GFAP staining, while neuronal survival was examined by Nissl staining. Luxol fast blue (LFB) staining, DAB staining, and western blot were adopted to evaluate the myelin loss. Basso-Beattie-Bresnahan (BBB) scoring and rump-height Index (RHI) assay was applied to evaluate locomotor functional recovery. RESULTS: Our data showed that HMGB1 can be elevated and released from necroptotic astrocytes and HMGB1 could induce pro-inflammatory microglia through the RAGE-nuclear factor-kappa B (NF-κB) pathway. We further demonstrated that inhibiting HMGB1 or RAGE effectively decreased the numbers of detrimental pro-inflammatory macrophages/microglia while increased anti-inflammatory cells after SCI. Furthermore, our data showed that inhibiting HMGB1 or RAGE significantly decreased neuronal loss and demyelination, and improved functional recovery after SCI. CONCLUSIONS: The data implicated that HMGB1-RAGE axis contributed to the dominant pro-inflammatory macrophages/microglia-mediated pro-inflammatory response, and inhibiting this pathway afforded neuroprotection for SCI. Thus, therapies designed to modulate immune microenvironment based on this cascade might be a prospective treatment for SCI.

A case report of thrombolysis resistance: thrombus ultrastructure in an ischemic stroke patient.

BACKGROUND: Following acute ischemic stroke (AIS), approximately half of patients do not achieve recanalization after intravenous administration of tissue plasminogen activator (rt-PA). Thrombolysis resistance is a possible reason for recanalization failure. Thrombolysis resistance is likely related to the ultrastructure and composition of the thrombus. However, there is a paucity of published information on the relationship between thrombus ultrastructure and thrombolysis resistance. CASE PRESENTATION: Two patients who underwent mechanical thrombectomy were observed within 4.5 h after stroke onset. One patient failed to respond to rt-PA (defined as thrombolysis resistant), and the other patient did not receive rt-PA treatment (non-rtPA). In each patient, the occluded artery was the internal carotid artery or middle cerebral artery. According to the Trial of ORG 10172 in Acute Stroke Treatment classification, both patients had large atherosclerotic cerebral infarction. By scanning electron microscopy (SEM) and transmission electron microscopy (TEM), we found that the thrombus structure was significantly different between the two patients. CONCLUSION: Grid-like dense fibrin, compressed polyhedral erythrocytes, and large accumulation of neutrophils may be characteristics of thrombolysis resistant thrombi.

Bilirubin: a novel predictor of hemorrhagic transformation and symptomatic intracranial hemorrhage after mechanical thrombectomy.

BACKGROUND AND PURPOSE: The role of bilirubin in patients treated with mechanical thrombectomy (MT) is unknown. We investigated the relationship between admission bilirubin levels and hemorrhagic complication in acute ischemic stroke (AIS) patients treated with MT and detailed the roles of direct bilirubin (DB), indirect bilirubin (IDB), and total bilirubin (TB). METHODS: Consecutive AIS patients treated with MT were enrolled from two stroke centers. Outcome measures included hemorrhagic transformation (HT) and symptomatic intracranial hemorrhage (sICH) within 48 h. An independent association of bilirubin with outcomes was identified by multivariate logistic regression analysis. The accuracies of bilirubin in predicting outcome were evaluated using receiver operating characteristic curve analysis. RESULTS: Of the 153 enrolled patients, 64 (41.8%) were diagnosed with HT, of which 28 (18.3%) had sICH. In univariate analyses, DB, IDB, and TB were higher in patients with HT and sICH than in patients without. After adjustment for potential confounders, DB (odds ratio [OR], 1.364; 95% confidence interval [CI], 1.133-1.641; p = 0.001), IDB (OR, 1.143; 95% CI, 1.052-1.242; p = 0.002), and TB (OR, 1.106; 95% CI, 1.041-1.175; p = 0.001) were independently associated with HT. IDB (OR, 1.177; 95% CI, 1.064-1.303; p = 0.002) and TB (OR, 1.102; 95% CI, 1.027-1.182; p = 0.007) were independently associated with sICH. Receiver operating characteristic curve analysis showed no significant difference between the three indicators of predicting HT and sICH. CONCLUSIONS: Elevated admission bilirubin is an independent predictor of HT and sICH in AIS patients treated with MT.

Comparation of vancomycin penetration into cerebrospinal fluid in postoperative intracranial infection and community-acquired meningitis patients.

WHAT IS KNOWN AND OBJECTIVE: To compare the penetration of vancomycin into cerebrospinal fluid (CSF) in patients with postoperative intracranial infection and community-acquired meningitis, and to identify related factors influencing the penetration in these two diseases. METHODS: The concentrations of vancomycin in serum and CSF were determined by enzyme amplified immunoassay, and the CSF-to-serum ratios were calculated. The correlation between CSF-to-serum ratios of vancomycin and CSF elements was analyzed. RESULTS AND DISCUSSION: In postoperative intracranial infection patients and community-acquired meningitis patients, the vancomycin concentration in CSF was 1.90 ± 1.29 mg/L and 2.47 ± 1.15 mg/L, while the CSF-to-serum ratio was 0.19 ± 0.12 and 0.26 ± 0.12, respectively. There was a significant correlation between vancomycin serum concentration and bodyweight (P < 0.05). The CSF-to-serum ratio in postoperative intracranial infection patients was correlated to white blood cell count in CSF. However, in community-acquired meningitis patients, no relationship was seen with regards to CSF white blood cell count, protein or glucose. WHAT IS NEW AND CONCLUSION: Cerebrospinal fluid vancomycin penetration was similar in postoperative intracranial infection and community-acquired meningitis patients. The CSF-to-serum ratio was only correlated to CSF white blood cell count in postoperative intracranial infection patients.

Angiotensin II and its receptor in activated microglia enhanced neuronal loss and cognitive impairment following pilocarpine-induced status epilepticus.

Neuroinflammation plays a role in the pathology of epilepsy and in cognitive impairment. Angiotensin II (AII) and the angiotensin receptor type 1 (AT1) have been shown to regulate seizure susceptibility in different models of epilepsy. Inhibition of AT1 attenuates neuroinflammatory responses in different neurological diseases. In the present study, we showed that the protein expression of AII and AT1 was increased in activated microglia following lithium pilocarpine-induced status epilepticus (SE) in rats. Furthermore, the AT1 receptor antagonist, losartan, significantly inhibited SE-induced cognitive impairment and microglia-mediated inflammation. Losartan also prevented SE induced neuronal loss in the hippocampus and exerted neuroprotection. These data suggest that losartan improves SE-induced cognitive impairment by suppressing microglia mediated inflammatory responses and attenuating hippocampal neuronal loss. Overall, our findings provide a possible therapeutic strategy for the treatment of cognitive impairment in epilepsy.

[Expression of vascular endothelial growth factor and microvessel density in different brain regions in aged rats].

OBJECTIVE: To observe the distribution of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in different brain regions in aged rats and determine the role of VEGF and MVD in the aging process of the nervous system. METHODS: We observed the expression of VEGF and MVD in different parts of rat brain in the 3- month group and 30-month group with immunohistochemical technique. RESULTS: Compared with the 3-month group, the 30-month group showed fewer VEGF-positive cells and MVD in the brain (P<0.01), and the number varied significantly in different brain regions (P<0.01). The motor cortex region contained more VEGF-positive cells and MVD than the hippocampus and cerebellum. CONCLUSION: VEGF-positive cells and MVD are decreased in every brain region of aged rats, and the motor cortex region contains more positive cells, suggesting exogenous VEGF may enhance the formation of microvessels and delay the aging of the nervous system.

Endovascular recanalization in patients with severely disabling non-acute ischemic stroke.

BACKGROUND: It is unclear whether patients with severely disabling ischemic stroke (SDIS-that is, modified Rankin scale (mRS) scores of 3-5) benefit from non-acute endovascular recanalization (ER). OBJECTIVE: To determine the effect of non-acute ER or medical treatment in severely disabled patients with non-acute ischemic stroke (mRS scores of 3-5). METHODS: Between January 2018 and August 2021, non-acute patients with SDIS and large vessel occlusion were collected from two regional stroke centers. Patients who met the inclusion and exclusion criteria were assigned to two groups based on whether they underwent ER (ER group) or not (medical group). The primary functional outcome was the mRS score at 90 days. The primary safety outcomes were the recurrence of stroke and mortality. RESULTS: Of the 325 patients with hypoperfusion cerebral infarction caused by large vessel occlusion, 63 met the inclusion criteria (32 patients in the ER group, 31 patients in the medical group). A favorable outcome (mRS score ≤2) occurred more often in the ER group than in the medical group (59.4% vs 22.6%, respectively; OR=0.12, 95% CI 0.02 to 0.58; P<0.01). There were no significant differences in new-onset ischemic stroke (6.3% vs 3.2%, respectively; P=1.000), symptomatic intracerebral hemorrhage (12.5% vs 0%, respectively; P=0.113), or mortality within 90 days (6.3% vs 6.5%, respectively; P=1.000) between the two groups. Preoperative mRS scores (OR=7.34, 95% CI 1.56 to 34.5; P=0.02) and ER (OR=0.12, 95% CI 0.02 to 0.58; P<0.01) were significantly associated with outcome. CONCLUSION: Our data suggest that patients with SDIS (mRS score 3-5) with smaller infarct cores and better collateral circulation can benefit from non-acute ER, with no additional perioperative complications or mortality.

[Characteristic of microglial activation of hippocampus in experimental epileptic rats].

OBJECTIVE: To investigate the characteristics of microglial activation of hippocampus in experimental epileptic rats. METHODS: Morphological changes and proliferation of OX-42 positive cells were compared at different time points after status of epilepticus (SE) in lithium-pilocarpine induced epileptic rats. RESULTS: OX-42 positive cells were activated after SE, which increased to a peak at 3-7 d and in a relatively stable state at 7-14 d; then gradually decreased after 14d and returned to slightly higher level than previously at 21 d. CONCLUSION: Inflammatory injury, microglial activation and cell proliferation are closely related after seizures, microglial activation may be an important mechanism in the inflammatory injury of epilepsy.

[Effect of Helicobacter pylori infection on platelet activation and coagulation function in patients with acute cerebral infarction].

OBJECTIVE: To investigate the effect of Helicobacter pylori (Hp) on platelet activation and coagulation function in patients with acute cerebral infarction. METHODS: Sixty-six patients with acute cerebral infarction and 50 health individuals were enrolled in the study. Hp antibody,expression of CD62p on platelets and clotting indexes were measured and compared between two groups. RESULTS: The positive rate of Hp-IgG and Hp-CagA in cerebral infarction patients were higher than that in controls (P<0.05). The positive rate of CD62p in patients with positive Hp-IgG and Hp-CagA was significantly higher than that in negative patients and also controls (P<0.05). The APTT and TT were lower and FIB was higher in patients with positive Hp antibody than those in patients with negative Hp antibody (P<0.05),but there was no difference in PT,PTR and INR (P>0.05). CONCLUSION: Hp infection can activate platelets and affect coagulation function,which may be involved in the development of cerebral infarction.

[The anti-aging effect of EPO and the preliminary probe into its mechanisms].

OBJECTIVE: To study whether erythropoietin ( EPO) has the anti-aging effect and the mechanisms of how it effects. METHODS: 5% D-galactose hypodermic injection for 6 weeks to establish the aging model. Divided rats into 5 groups randomly: the normal control (group A), the aging model (group B), the low dosage (1 000 U/ (kg x d)) of recombinant human erythropoietin (rhEPO) intervene (group C), the middle dosage (3 000 U/(kg x d)) of rhEPO intervene (group D) and the high dosage (5 000 U/(kg x d)) of rhEPO intervene (group E), 10 rats in each group. Morris water maze was used to comparing the behavioral indexes. After decapitating the rats, the malonaldehyde (MDA), Na(+)-K+ ATPase, total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) of brain tissue were tested. One rat from each group was selected randomly to observe the hippocampal ultramicrostructure. RESULTS: (1) Compared with group A, the learning and memory ability of group B reduced, the level of MDA, the Na(+)-K+ ATPase, T-AOC and the SOD activities of brain tissue decreased (P < 0.05), besides, a series of aging changes were observed in the hippocampal ultramicro-structure in group B. (2) Compared with group B, an improved learning and memory ability of group D, a reduced MDA content and an increased activity of Na(+)-K+ ATPase, T-AOC and the SOD activities of brain tissue in group D were also observed with a improved hippocampal ultramicro-structure. (3) The low dosage of rhEPO intervention could against the decrease of the activities of brain Na(+)-K+ ATPase, SOD of aging rat (P < 0.05), but had no significant effects on the rest of the indicators. The high dosage of rhEPO intervention had no significant improvements on various indicators of aging rats in high dosage of rhEPO intervention group was noticed (P > 0.05). CONCLUSION: The middle dosage of EPO has the anti-aging effect, and its mechanisms may be related to enhancing the antioxidant enzymes activity and increasing the antioxidant capacity.

rhEPO Upregulates the PPARγ Pathway in Long-term Cultured Primary Nerve Cells via PI3K/Akt to Delay Cell Senescence.

Previous studies have confirmed that both recombinant human erythropoietin (rhEPO) and peroxisome proliferator-activated receptors γ (PPARγ) activator pioglitazone can protect senescent nerve cells, and their mechanisms involve enhancing cell antioxidant capacity and reducing cell apoptosis. However, whether the PPARγ pathway is involved in the rhEPO anti-aging process in neuronal cells is still unclear. In this study, to explore the relationship between rhEPO and the PPARγ pathway at the cellular level, primary nerve cells cultured for 22 days were used to simulate the natural aging process of nerve cells. Starting on the 11th day of culture, rhEPO, LY294002, and GW9662 were added for treatment. Immunochemical methods and SA-ß-gal staining were used to observe the changes in cellular antioxidant capacity and the fraction of senescent cells. The results showed that PPARγ blockade retarded the effect of rhEPO on the cellular antioxidant capacity and altered the fraction of senescent cells. It was confirmed that PPARγ was involved in rhEPO's anti-aging process in neuronal cells. Real-time fluorescent quantitative RT-PCR, Western blotting, and immunofluorescence staining were used to observe the changes in PPARγ pathway-related factors in nerve cells after rhEPO treatment. The results showed that rhEPO significantly upregulated the expression of PPARγ coactivator-1α (PGC-1α), PPARγ, and nuclear PPARγ in cells but did not affect the level of phosphorylated PPARγ protein, confirming that rhEPO has the ability to upregulate the PPARγ pathway. PI3K/Akt and PPARγ pathway blockade experiments were used to explore the relationships among rhEPO, PI3K/Akt, and PPARγ. The results showed that after PPARγ blockade, rhEPO had no significant effect on the PI3K/Akt pathway-related factor p-Akt, while after PI3K/Akt blockade, rhEPO's effects on PPARγ-related factors (PGC-1α, PPARγ, and nuclear PPARγ) were significantly decreased. It is suggested that rhEPO delays the PI3K/Akt pathway in the process of neuronal senescence, which is located upstream of PPARγ regulation. In conclusion, this study confirmed that rhEPO can upregulate the expression of PGC-1α and PPARγ in cells and the level of PPARγ protein in the nucleus to enhance the antioxidant capacity of cells and delay the senescence of nerve cells through the PI3K/Akt pathway. These findings will provide ideas for finding new targets for neuroprotection research and will also provide a theoretical basis and experimental evidence for rhEPO anti-aging research in neural cells.

Recombinant human erythropoietin protects long-term cultured ageing primary nerve cells by upregulating the PI3K/Akt pathway.

OBJECTIVE: Previous studies have found that recombinant human erythropoietin (rhEPO) protects long-term cultured ageing primary nerve cells by enhancing the endogenous antioxidant capacity of cells; however, its signalling pathways are not clear. This study aimed to explore the relationship between the rhEPO and PI3K/Akt pathways in the protection of senescent nerve cells at the cellular level. METHODS: Primary nerve cells were cultured for 22 days to mimic the natural ageing process of nerve cells. rhEPO and LY294002 were administered as an intervention on the 11th day of culture. Western blot, immunochemistry, 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide, immunofluorescence double-labelling staining, Annexin V-FITC/PI double-labelling flow cytometry, and SA-ß-gal staining experiments were used to observe the expression levels of erythropoietin receptor (EPOR) and phosphorylated Akt (p-Akt) protein and the related indices of nerve cell senescence. RESULTS: Western blot experiments showed that in ageing long-term cultured primary neurons, the EPOR and p-Akt decreased and rhEPO upregulated the expression levels of EPOR and p-Akt protein. The rest showed that the PI3K/Akt pathway blockade reduced the antioxidation capacity, cell viability, cell morphology, and ratio of apoptotic cells and senescent cells of rhEPO on ageing long-term cultured primary nerve cells. CONCLUSIONS: This study explored the relationship between the rhEPO and PI3K/Akt pathways in the protection of ageing nerve cells at the cellular level and found that rhEPO protects long-term cultured ageing primary nerve cells by upregulating the PI3K/Akt pathway. These findings provide a theoretical basis and experimental evidence for the antiaeging mechanism of EPO in the nervous system.

[Effect of puerarin on the expression of NMDA receptor in the hippocampus CA1 region after focal cerebral ischemia in rats].

OBJECTIVE: To study the antagonistic action of Puerarin against the excitatory amino acid toxicity, and to further explore its brain protection mechanisms. METHODS: Focal cerebral ischemia model was set up with middle cerebral artery occlusion by intraluminal block in this study. After cerebral ischemia, Puerarin was administered at different time point. The volume of cerebral ischemia was assessed by TTC stain. NR1 positive neurons in hippocampus CA1 region was determined by immunohistochemistry SABC method. RESULTS: The cerebral ischemia volumes were smaller in 2 h and 12 h model treatment groups (P < 0.05) than those in model control groups, but no significant differences were observed in 24 h model treatment group. Compared with sham-operation group, the NR1-positive cells in hippocampal CA1 region were increased obviously (P < 0.05) in both model control and model treatment groups. Compared with model control groups, the NR1-positive cells in hippocampal CA1 were decreased obviously (P < 0.05) in 2 h and 12 h treatment groups. CONCLUSION: The treatment of Puerarin within 12 h after ischemia can cut down the expression of NMDA receptor. This indicates that the puerarin treatment in earlier period after ischemia can indirectly rivalry toxic effect of excitatory amino acids, relieve neural injury.

Research on multi decision making security performance of IoT identity resolution server based on AHP.

The application scenarios of IoT (Internet of Things) are complex and diverse. Failure of security defense in any part of IoT can lead to huge information leakage and incalculable losses. IoT security issues are affecting and limiting its application prospects, and have become one of the hotspots in the field of IoT. Identity resolution security of IoT has become a core issue in solving the security problem of IoT. The aim of this paper is to apply AHP, a well-known decision making method, to IoT identity resolution security. Selecting 6 indicators, several pairwise comparison matrices are constructed based on scores from experts and lab researchers. The AHP method is used to calculate malicious resolution value as a quantitative basis for judging the security performance of each resolution server. An experimental case is used to verify the validity and correctness of the AHP-based IoT identity resolution security evaluation model.

Direct versus Bridging Mechanical Thrombectomy in Elderly Patients with Acute Large Vessel Occlusion: A Multicenter Cohort Study.

PURPOSE: Elderly people represent a growing stroke population with different pathophysiological states than younger. Whether intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is beneficial for elderly patients remains unclear. This study compared the efficacy and safety between elderly patients treated with MT alone and those treated with both IVT and MT. PATIENTS AND METHODS: Patients aged ≥65 years who were eligible for IVT within 4.5 h from symptom onset were selected from the ANGEL-ACT (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke) registry, a prospective registry program for patients with endovascular treatment from 111 Chinese stroke centers. The primary efficacy outcome was the 90-day modified Rankin Scale score. We compared efficacy and safety outcomes using ordinal or binary logistic regression or a generalized linear model. RESULTS: In total, 482 elderly patients were included: 187 (38.8%) received IVT and MT (bridging MT) and 295 (61.2%) received MT alone (direct MT). There was no significant difference in the 90-day modified Rankin Scale score between the two groups (median: 4 vs 4 points, respectively; adjusted ß=-0.048, P=0.822). The direct MT group had a shorter onset-to-puncture time (225 vs 255 min, respectively; adjusted ß=-55.074, P=0.002) and a lower rate of parenchymal hemorrhage type 2 within 24 h (2.80% vs 6.63%, respectively; adjusted odds ratio [OR]=0.287, 95% confidence interval [CI]=0.096-0.856, P=0.025). In addition, the direct MT group showed a trend toward a lower incidence of sICH (5.67% vs 10.06%, adjusted OR=0.453, P=0.061), procedure-related complications (7.12% vs 12.30%, adjusted OR=0.499, P=0.052) and distal or new territorial embolization (4.07% vs 6.95%, adjusted OR=0.450, P=0.093). CONCLUSION: Direct MT had similar efficacy to bridging MT in terms of the 90-day functional outcome in elderly patients, whereas bridging MT had a longer onset-to-puncture time and increased risk of hemorrhagic transformation and procedure-related complications.

[Expression of vascular endothelial growth factor and microvessel density in hippocampus of rats with aging].

OBJECTIVE: To investigate the expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in hippocampus of rats with aging. METHODS: Paraffin sections of brain tissue of rats at the age of 3, 18, 24, 30 months were stained by immunohistochemistry, the expression of VEGF and MVD was quantitatively analyzed. RESULTS: Innunohistochemical staining showed that the VEGF-positive cells were mainly pyramidal neuron in hippocampus; the intensity of VEGF-positivity in neuron cells was decreased with the aging (P<0.05). The MVD in hippocampus was also decreased with the aging of rats (P<0.05). CONCLUSION: Increasing VEGF contents and improving blood circulation in brain tissue may prevent or treat vascular dementia and cerebrovascular diseases.

[Expression of GLUT 3 in different brain regions of aged rats].

OBJECTIVE: To examine the distribution of glucose transport 3 (GLUT 3) in different brain regions of aged rats and to investigate its role in ageing process of the nervous system. METHODS: The GLUT 3 expression in different brain regions was examined with immunohistochemical method in rats aged 3, 18 and 30 months, respectively. RESULTS: The number of GLUT 3-positive cells varied in the different brain regions in rats of all age groups (P<0.01); the CA1 region contained the greatest number of positive cells,and fewer in the motor cortex and cerebellum. The number of GLUT 3-positive cells was reduced in the brain of aged rats (P<0.01); and the neural cells in 4 different brain regions presented with large cell body and loose alignment. CONCLUSION: The expression of GLUT 3 decreased in aged rats, which suggests that GLUT 3 may be involved in the ageing process of nervous system.

[Hypoxia inducible factor-1alpha expression trends in hippocampus of rat of different ages].

OBJECTIVE: To reveal the expression trends of HIF-1alpha in hippocampus of different age rats, investigate the role of HIF-1alpha in the aging process of nervous system. METHODS: The cerebral tissues was collectd from rats of different age, including 3, 18, 24, 36 months old. There were 6 rats in each age group. The expressions of nissl body and HIF-1alpha in different part of hippocampus were observed by nissl staining and immunohistochemical technique. RESULTS: (1) With the increase of rat age, nerve cells appeared to be bigger and to arrange sparsely, while the nissl body decreased; (2) The positive HIF-1alpha staining cells in CA1, CA3 region of hippocampus increased along with the increase of rat age. The difference between any two age groups showed statistical significance (P < 0.05). CONCLUSION: The function of protein synthesis weakened in nerve cells but the expression of HIF-1alpha increased with the age increasing, which may play an important role in aging of nervous system.

[Expression of hypoxia inducible factor-1alpha and erythropoietin in the hippocampus of aging rats].

OBJECTIVE: To explore the expression of hypoxia inducible factor-1alpha (HIF-1alpha) and erythropoietin in the hippocampus of aging rats, and to investigate the role of HIF-1alpha and erythropoietin in the aging of nervous system. METHODS: The expression of Nissl body, HIF-1alpha, and erythropoietin in the CA1 region of the hippocampus in different months was observed by Nissl staining and immunohistochemical technique. RESULTS: Nerve cells became bigger and appeared sparse, and the Nissl bodies decreased with age. HIF-1alpha positive cells increased significantly with age in the CA1 region of the hippocampus (P<0.05). The expression of erythropoietin presented a parabola with aging in the CA1 region of the hippocampus. The increase from 3 to 18 months and the reduction from 18 to 30 months of erythropoietin positive cells had statistical significance (both P<0.05). CONCLUSION: HIF-1alpha and erythropoietin are parallelly incremental before middle age, and are separated after middle age, suggesting decreased activity of HIF-1alpha and recession of protein synthesis function may be the main reasons for decreased expression of erythropoietin in the brain during aging. Strengthened endogenous HIF-1alpha activity and supply of exogenous erythropoietin may delay the aging of the nervous system.