Neural pathway participates in protection of limb ischemic preconditioning against brain injuries induced by ischemia/reperfusion in rats / 中国应用生理学杂志

<p><b>AIM</b>To explore the role of femoral nerves section (FNS) on the protection of limb ischemic preconditioning (LIP) against cerebral ischemia/reperfusion injuries.</p><p><b>METHODS</b>Model of brain ischemia induced by Four-vessel occlusion was used. LIP was performed by clamping the bilateral femoral arteries for 10 min 3 times in a interval of 10 min. Rats with vertebral arteries permanently occluded were divided into sham group, cerebral ischemic group, FNS + cerebral ischemic group, LIP + cerebral ischemic group, FNS + LIP + cerebral ischemic group. The changes of neural density (ND) in the CA1 hippocampus were observed 7d after the sham operation or brain ischemia under thionin staining. The expression of c-Fos in the CA1 hippocampus was measured 6 h after the sham operation or brain ischemia under immunohistochemistry method.</p><p><b>RESULTS</b>Thionin staining revealed that serious neuronal damage was visualized in the CA1 hippocampus in both cerebral ischemic group and FNS + cerebral ischemic group as compared with sham group. LIP attenuated the neuronal damage of the CA1 subfield induced normally by cerebral ischemia/reperfusion, and ND in LIP + cerebral ischemic group was significantly higher than that in cerebral ischemic group (P < 0.01). But obvious neuronal damage of the CA1 subfield was found in FNS+ LIP + cerebral ischemic group, and ND was significantly decreased as compared with LIP + cerebral ischemic group (P < 0.01). These results suggested that the protection of LIP against cerebral ischemia/reperfusion injuries might be cancelled by preceding section of femoral nerve. It was found that there was almost no c-Fos expression in the CA1 hippocampus in sham group. Changes of c-Fos expression in the CA1 subfield in cerebral ischemic group were similar to that in sham group. But in LIP + cerebral ischemic group, c-Fos expression in the CA1 subfield was markedly increased and the number of positive cells and optical density of c-Fos expression were significantly higher than those in sham and cerebral ischemic group. c-Fos expression in the CA1 subfield was again decreased in FNS + LIP + cerebral ischemic group, and the number of positive cells and optical density of c-Fos expression were significantly lower than those in LIP + cerebral ischemic group.</p><p><b>CONCLUSION</b>Neural pathway participated in the protective effect of LIP on brain, and increased c-Fos expression in the CA1 hippocampus by LIP after cerebral ischemia/reperfusion, might be a part of neural pathway by which LIP induced brain ischemic tolerance.</p>

The effect of time parameters of cerebral ischemic preconditioning on its protective effect against global cerebral ischemic injury in rats / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effects of the duration of cerebral ischemic preconditioning(CIP) and interval between CIP and the subsequent ischemic insult on the protection of CIP against delayed neuronal death (DND) in the CA1 hippocampus normally induced by brain ischemic insult.</p><p><b>METHODS</b>Four-vessel occlusion cerebral ischemic model of rats (54) was used. The brain of the rats was sectioned and stained with thionin to show DND in the CA1 hippocampus.</p><p><b>RESULTS</b>No DND was found in the hippocampus of the rats subjected to sham operation and CIP, in which 3 min cerebral ischemic preconditioning was performed. Obvious destruction of the CA1 hippocampus was found in brain ischemic insult group, in which histological (HG) was 2-3 in 6 min and 10 min ischemia subgroups and grade 3 in 15 min ischemia subgroup. In CIP + brain ischemic insult group, no obvious neuronal damage was found in 3 min-3d-6 min (CIP for 3 min was followed by a brain ischemic insult for 6 min at an interval of 3 d, the same as the following) and 3 min-3 d-10 min groups, indicating that CIP effectively protected neurons of the CA1 hippocampus against DND normally induced by ischemic insult for 6 or 10 min. However, in 3 min-1 d-10 min and 3 min-3 d-15 min groups, the protective effect of CIP was lower than that in the 3 min-3 d-10 min group. The quantitative analysis of the protective effect of CIP on the CA1 hippocampal neurons showed that there was no significant difference in protecting number and protecting index between 3 min-3 d-6 min and 3 min-3 d-10 min groups (P > 0.05). However, the growth index in 3 min-3 d-10 min group was obvious larger than that in 3 min-3 d-6 min (P < 0.05).</p><p><b>CONCLUSION</b>Although the protective effects of CIP in 3 min-3 d-6 min and 3 min-3 d-10 min groups were similar, the protective effect of CIP in 3 min-3 d-10 min group was sensitively found. Maximal protective potential of CIP could be induced when using the time parameters of 3 min-3 d-10 min to establish the model of global cerebral ischemic tolerance.</p>

Limb ischemic preconditioning decreases hippocampal ischemia/reperfusion injuries in rats / 中国应用生理学杂志

<p><b>AIM</b>To explore the effects of limb ischemic preconditioning (LIP) on cerebral ischemia/reperfusion injuries.</p><p><b>METHODS</b>Thirty six wistar rats, of which bilateral vertebral arteries were occluded permanently, were randomly divided into the following 6 groups: control group, cerebral ischemic group, limb ischemic group, LIP 0 d group (cerebral ischemia was given immediately after LIP), LIP 1 d group (cerebral ischemia was given 1 d after LIP) and LIP 2 d group (cerebral ischemia was given 2 d after LIP). Global cerebral ischemia was performed by four vessels occlusion in rats. LIP was performed by occluding the bilateral femoral arteries for 10 min 3 times in a interval of 10 min. The histological grade and pyramidal neuronal density in the CA1 hippocampus were measured to quantitate the degree of hippocampal injury under thionin staining.</p><p><b>RESULTS</b>The histological grade was increased and the pyramidal neuronal density was decreased in the CA1 hippocampus of the cerebral ischemic group (P < 0.01). The damage of the CA1 hippocampus in LIP 0 d group was significantly diminished, which represented by decreased histological grade and increased neuronal density compared with the cerebral ischemic group (P < 0.01). But the CA1 hippocampus still showed obvious injuries in the LIP 1 d and LIP 2 d group.</p><p><b>CONCLUSION</b>LIP performed immediately prior to cerebral ischemia could confer obvious protective effects on CA1 hippocampus against cerebral ischemia/reperfusion injuries. But LIP performed 1 d and 2 d prior to cerebral ischemia could not afford the protection against injuries induced by cerebral ischemia/reperfusion.</p>

Limb ischemic preconditioning attenuates apoptosis of pyramidal neurons in the CA1 hippocampus induced by cerebral ischemia-reperfusion in rats / 生理学报

The purpose of this study was to investigate the effects of limb ischemic preconditioning (LIP) on apoptosis of pyramidal neurons in the CA1 hippocampus induced by global cerebral ischemia-reperfusion in rats. Forty-six rats whose bilateral vertebral arteries were occluded permanently were assigned to one of four groups: sham group, limb ischemia group, cerebral ischemia group and LIP group. LIP was performed by occluding the bilateral femoral arteries for 10 min 3 times in an interval of 10 min. Global cerebral ischemia was underwent by occluding the bilateral common carotid arteries for 8 min immediately after LIP. Assays for apoptosis of the hippocampal neurons were biologically and morphologically performed using gel electrophoresis, TUNEL and AO/EB staining. Characteristic DNA ladder was clearly visualized with gel electrophoresis in the hippocampus in cerebral ischemia group, but not in LIP group. The number of TUNEL-positive cells in the CA1 hippocampus was significantly reduced by LIP from 69.8+/-12 (cerebral ischemia group) to 17.8+/-5.8 (P<0.01). AO/EB staining also showed a reduction of apoptosis in LIP group compared with cerebral ischemia group. These results suggest that LIP can inhibit hippocampal neuronal apoptosis induced by cerebral ischemia-reperfusion, which contributes to the protection against the delayed neuronal death induced by cerebral ischemic insult.

Dynamic Changes of Hydrogen Sulfide in Cortical Tissues of Neonatal Rats with Hypoxia-Ischemia Brain Damage / 实用儿科临床杂志

Objective To explore the dynamic changes of hydrogen sulfide(H2S)in the pathological course in cortical tissues at diffe-rent times of hypoxia-ischemia brain damage(HIBD).Methods Fifty-six healthy 7-day-old Sprague-Dawley newborn rats were randomly assigned into 7 groups(n=8):normal group,sham-operated group,HIBD 12 h group,HIBD 24 h group,HIBD 48 h group,HIBD 72 h group,and HIBD 7 d group.HIBD rat models were established by ligating the left common carotid artery,after 2-4 h,followed by exposuring to hypoxia(80 mL/L oxygen and 920 mL/L nitrogen)for 2 h.The achievement of HIBD model was determined by the change on behaviour of neonatal rats.There were no treatment on the normal group,and the left common carotid artery was only separated in the sham group.The left cortical tissues in the experimental group were removed at 12,24,48,72 h,and 7 d after HIBD.H2S amounts in cortical tissues at different times after HIBD were measured by biochemical methods.Results H2S level in cortical tissues in HIBD 12 h group increased significantly compared with sham-operated group(P

Effect of nitric oxide synthase inhibitor L-NAME on the induction of brain ischemic tolerance in rats / 生理学报

To explore the role of NO in the induction of brain ischemic tolerance (BIT) in vivo, the effect of nitric oxide synthase (NOS) inhibitor L-NAME on the induction of BIT induced by cerebral ischemic preconditioning (CIP) was investigated in the hippocampal CA1 subfield in CIP and ischemic insult models established by rat four-vessel occlusion using brain tissue section and thionine staining methods. Fifty-four male Wistar rats were divided into 6 groups: (1) sham-operated group (n=6): bilateral common arteries were separated without occluding the cerebral blood flow; (2) ischemia group (n=6): an ischemic insult for 10 min was given; (3) CIP+ischemia group (n=6): 3-min CIP was preformed 72 h prior to 10-min ischemic insult; (4) L-NAME group (total n=24, n=6 for each subgroup): L-NAME (5 mg/kg, i.p.) was administered 1 h prior to CIP and 1, 12 and 36 h after CIP, respectively. Other procedures were the same as those for the CIP+ischemia group; (5) L-NAME+L-Arg group (n=6): L-NAME (5 mg/kg, i.p.) and L-Arg (300 mg/kg, i.p.) were administered 1 h prior to CIP, other procedures were the same as those for the L-NAME group; (6) L-NAME+ischemia group (n=6): L-NAME (5 mg/kg, i.p.) was administered 72 h before the 10-min ischemic insult. The results showed that (1)10-min ischemic insult resulted in an increase in the histological grade (indicating a more serious tissue injury) and a decrease in pyramidal neuronal density (P<0.01); (2) the histological grade and neuronal density in hippocampal CA1 in the CIP+ischemia group were similar to those in the sham-operated group (P>0.05); (3) in the L-NAME group, administration of L-NAME brought about an increase in the histological grade and a decrease in neuronal density (P<0.01), suggesting that L-NAME blocked the protection of CIP; (4) the neuronal damage in L-NAME+L-Arg group was slighter than that in the L-NAME group, but still more serious than that in the CIP+ischemia group, suggesting that L-Arg partly reversed the blocking effect of L-NAME; (5) the morphological representations in L-NAME+ischemia group were basically similar to those in the ischemia group. The results mentioned above indicate that NO is involved in the induction of BIT in vivo. The blocking effect of L-NAME administered at 36 h after CIP was obviously weaker than the effects of L-NAME administered 1 h prior to CIP, and 1 or 12 h after CIP. It is suggested that NO is involved in the induction of BIT at an early stage and that the involvement might take place via activating cascades of the events.

Effects of alpha-methyl-(4-tetrazolyl-phenyl) glycine on the induction of hippocampal ischemic tolerance in the rat / 生理学报

To explore the role of metabotropic glutamate receptor 2/3 mGluR 2/3 in the induction of brain ischemic tolerance (BIT), the influences of mGluR2/3 antagonist alpha-methyl-(4-tetrazolyl-phenyl) glycine (MTPG) on the induction of BIT and expression of glial fibrillary acidic protein (GFAP) in the hippocampus were observed using thionin staining and GFAP immunohistochemical staining in a rat brain ischemic model with four-vessel occlusion (4VO). Fifty-four rats, of which bilateral vertebral arteries were occluded permanently by electrocautery, were divided into 5 groups: (1) sham operated group (n=8): the bilateral carotid common arteries (BCCA) were separated, but the blood flow was not blocked; (2) ischemia group (n=8): the blood flow of BCCA was blocked for 8 min; (3) ischemic preconditioning (IP) group (n=8): the blood flow of BCCA was occluded for 3 min as a cerebral ischemic preconditioning (CIP), and then the rats were exposed to an 8-min brain ischemic insult 24 h after the CIP; (4) MTPG+IP group (n=22): MTPG was administered 20 min before the CIP, then the rats were exposed to an 8-min brain ischemia insult 24 h after the CIP. In order to examine dosage dependency in the effect of MTPG, 4 dosages of MTPG (0.4, 0.2, 0.04 and 0.008 mg) were administered; (5) MTPG+ischemia group (n=8): an ischemic insult for 8 min was given 24 h after the administration of MTPG (0.2 mg). MTPG was injected into the right lateral cerebral ventricle. The results obtained are as follows. (1) Ischemic insult for 8 min increased the histological grade (HG) and reduced the neuronal density (ND) significantly, and also increased the expression of GFAP significantly (P<0.05 vs sham-operated group). (2) In the IP group, the above changes were not observed, indicating that CIP could protect pyramidal neurons against the ischemic insult. (3) The protective effects of CIP were blocked by MTPG, as manifested by the significant increase in HG and decrease in ND in the MTPG+IP group (P<0.05 vs sham-operated group). The changes were dose-dependent. (4) No obvious difference in the HG, ND and expression of GFAP was detected between the groups of MTPG+ischemia and ischemia. The above results indicate that MTPG blocks the induction of BIT induced by CIP, suggesting that mGluR2/3 participates in the induction of BIT.

Effects of Progesterone on Brain Damage in Hypoxia Mouse / 实用儿科临床杂志

Objective To observe the changes of water, potassium and sodium in the hypoxic cerebral tissues in mice and the effects of progesterone on the tissues and investigate the neuroprotective role of progesterone (PROG)in the cerebral anoxia. Methods Thirty - two male mice were divided into control group, simple hypoxia group, lower dosage group and higher dosage group. Progesterone was injected intraperitoneally in the dosage of 4 mg/kg or 8 mg/kg respectively 30 min before hypoxia in the last two groups. The contents of water, potassium and sodium in brain tissues in mice were evaluated at 24 hours after cerebral anoxia. Results The water, potassium and sodium contents in simple hypoxia group were significantly higher than those in control group(P0.05)in higher dosage group(8 mg/kg PROG)compared with those of simple hypoxia group. Conclusions At 24 hours after cerebral anoxia, there are significant increases of water, potassium and sodium in brain tissues. Progesterone may pro-duce neuroprotective role by inbibiting the rise of them.

Effects of the metabotropic glutamate receptor ligand(s)-4C3HPG on the induction of brain ischemic tolerance in the rat / 中国应用生理学杂志

<p><b>AIM</b>To explore roles of metabotropic glutamate receptor1/5 (mGluR1/5) in the induction of brain ischemic tolerance (BIT) induced by cerebral ischemic preconditioning (CIP), influences of mGluR1/5 ligand (s)-4-carboxy-3-hydroxy- phenylglycine ((s)-4C3HPG) on the induction of BIT and expression of glial fibrillary acidic protein (GFAP) in the hippocampus were observed.</p><p><b>METHODS</b>Thionin staining and GFAP immunohistochemistry staining in rat 4 vessel occlusion (4VO) brain ischemic model was used. Thirty-six rats, of which bilateral vertebral arteries were occluded permanently by electrocautery, were divided into the following 4 groups: sham group; ischemic insult group, BIT group and (s)-4C3HPG group. According to dosages of (s)-4C3HPG used, the (s)-4C3HPG group, was further divided into 0.2 mg, 0.04 mg and 0.008 mg subgroups. All the rats were killed 7 d after the operation or the final ischemic treatment.</p><p><b>RESULTS</b>(1) The ischemic insult for 8 min increased the histological grade (HG), decreased the pyramidal neuronal density (ND) and increased the expression of GFAP significantly (P < 0.05 vs sham) (2) The CIP prevented the above injury changes in the BIT group. (3) The protective effects of the CIP were blocked by (s)-4C3HFG, as manifested by significant increases in HG and decreases in ND in the (s)-4C3HPG group (P < 0.05 vs sham and BIT groups). The changes were proportional with the dosages of (s)-4C3HPG used.</p><p><b>CONCLUSION</b>(s)-4C3HPG could block the induction of BIT induced by CIP, suggested that mGluR1/5 participate in the induction of BIT.</p>