Biomedical subjects

Satoshi Takeo

Publications and source records attributed to Satoshi Takeo.

At least 37 records · Page 2Linked to original sources

PubMed2005

Preferable anesthetic conditions for echocardiographic determination of murine cardiac function.

Ketamine and xylazine are routinely used for measurement of hemodynamics of mice and rats by echocardiography. The anesthetic agents produce low heart rate (HR) in the animals, which may result in misleading data in the hemodynamic profiles of the small animals. The purpose of the present study was to select an appropriate anesthetic condition in the evaluation of mouse and rat cardiac function by echocardiography. Echocardiographic measurement was performed in male C57BL6 mice anesthetized with an intraperitoneal injection of 30 or 40 mg/kg pentobarbital (P30 or P40) or a combination of 60 mg/kg ketamine and 6 mg/kg xylazine (KX) and in male Wistar rats with an intraperitoneal injection of 40 or 50 mg/kg pentobarbital (P40 or P50) or a combination of 100 mg/kg ketamine and 10 mg/kg xylazine (KX). Basal HR of P30-anesthetized mice and P40-anesthetized were comparable to those in the conscious state, whereas KX-anesthetized mice and rats were 38% and 74% of those of the conscious animals, respectively. Fractional shortening (FS) and cardiac output index (COI) of the P30-anesthetized mice or the P40-anesthetized rats were greater than those of KX-anesthetized animals. Intraperitoneal injection of dobutamine at 0.3 and 1 mg/kg increased HR, FS, and COI of the P30-anesthetized mice and the P40-anesthetized rats, respectively, whereas the percent responses of these parameters in KX animals were greater than those in pentobarbital-anesthetized ones due to the lower basal values for the cardiac functional parameters. Anesthesia with P30 for the mouse and P40 for the rat rather than ketamine/xylazine may be relevant to the evaluation of cardiac function using echocardiography.

Adrenergic beta-Agonists↗

PubMed2004

Effects of nefiracetam on the levels of brain-derived neurotrophic factor and synapsin I mRNA and protein in the hippocampus of microsphere-embolized rats.

Our recent study demonstrated that nefiracetam, N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide, prevented impairment of the cyclic AMP (cAMP)/cAMP-responsive element binding (CREB) protein signaling pathway in sustained cerebral ischemia. The purpose of the present study was to determine whether nefiracetam has an effect on the expression of brain-derived neurotrophic factor (BDNF) and synapsin I mRNAs that are believed to be produced via CREB, and the alteration in their protein contents in the hippocampus after cerebral ischemia. Sustained cerebral ischemia was induced by injection of 700 microspheres into the right hemisphere of each rat. The rats were treated once daily with 10 mg/kg nefiracetam, p.o., from 15 h after the operation. Treatment with nefiracetam reduced the prolongation of the escape latency in the water maze test on days 7-9 after microsphere embolism-induced sustained cerebral ischemia, suggesting an improvement in the spatial learning function. Microsphere-embolized rats on day 5 showed decreases in BDNF and synapsin I mRNA levels and their protein contents in the ipsilateral hippocampus. Treatment with nefiracetam partially attenuated the decreases. These results suggest that enhancement of BDNF and synapsin I expression by nefiracetam treatment may be, at least in part, due to the improvement in the CREB binding activity, contributing to the prevention of learning and memory dysfunction after sustained cerebral ischemia.

Animals↗

PubMed2004

Two alpha1-adrenergic receptor subtypes regulating the vasopressor response have differential roles in blood pressure regulation.

To study the functional role of individual alpha1-adrenergic (AR) subtypes in blood pressure (BP) regulation, we used mice lacking the alpha1B-AR and/or alpha1D-AR with the same genetic background and further studied their hemodynamic and vasoconstrictive responses. Both the alpha1D-AR knockout and alpha1B-/alpha1D-AR double knockout mice, but not the alpha1B-AR knockout mice, had significantly (p < 0.05) lower levels of basal systolic and mean arterial BP than wild-type mice in nonanesthetized condition, and they showed no significant change in heart rate or in cardiac function, as assessed by echocardiogram. All mutants showed a significantly (p < 0.05) reduced catecholamine-induced pressor and vasoconstriction responses. It is noteworthy that the infusion of norepinephrine did not elicit any pressor response at all in alpha1B-/alpha1D-AR double knockout mice. In an attempt to further examine alpha1-AR subtype, which is involved in the genesis or maintenance of hypertension, BP after salt loading was monitored by tail-cuff readings and confirmed at the endpoint by direct intra-arterial recording. After salt loading, alpha1B-AR knockout mice developed a comparable level of hypertension to wild-type mice, whereas mice lacking alpha1D-AR had significantly (p < 0.05) attenuated BP and lower levels of circulating catecholamines. Our data indicated that alpha1B- and alpha1D-AR subtypes participate cooperatively in BP regulation; however, the deletion of the functional alpha1D-AR, not alpha1B-AR, leads to an antihypertensive effect. The study shows differential contributions of alpha1B- and alpha1D-ARs in BP regulation.

Animals↗

PubMed2004

Hepatocyte growth factor improved learning and memory dysfunction of microsphere-embolized rats.

Hepatocyte growth factor (HGF), an organotropic factor for regeneration and protection in various organs, has the ability to attenuate cerebral ischemia-induced cell death. The effect of HGF on learning and memory function after cerebral ischemia, however, remains unknown. We have demonstrated that administration of human recombinant HGF (hrHGF) into the ventricle reduced prolongation of the escape latency in acquisition and retention tests of the water maze task on Days 12-28 after microsphere embolism-induced cerebral ischemia. Treatment with hrHGF also attenuated the decrease in viable area and the density and number of perfused cerebral vessels, particularly those with a diameter smaller than 10 microm, of the ipsilateral hemisphere on Day 28 after the cerebral ischemia. We observed that treatment with hrHGF reduced the number of TUNEL-positive cerebral endothelial cells at the early stage after the ischemia. These results suggest that hrHGF prevents learning and memory dysfunction seen after sustained cerebral ischemia by protecting against injury to the endothelial cells. HGF treatment may be a potent therapeutic strategy for cerebrovascular diseases, including cerebral infarct and vascular dementia.

Analysis of Variance↗

PubMed2004

Modulation of G-protein expression and adenylyl cyclase signaling by high glucose in vascular smooth muscle.

OBJECTIVE: We have recently shown a decreased expression of Gialpha proteins and associated functions in aorta from short term (5 days) streptozotocin-induced diabetic rats. Since hyperglycemia is one of the underlying causes of diabetes-induced cardiovascular complications, it was of interest to examine if hyperglycemia may play a direct role in down regulating the expression of Gialpha in vascular smooth muscle cells of diabetic subjects. For this, the effect of high glucose treatment on Gialpha protein expression and adenylyl cyclase signaling in intact aorta and vascular smooth muscle cells (A10 cells) was investigated. METHODS: The cells were grown in normal glucose (5.5 mM) medium and were subsequently exposed to high glucose (26 mM) or normal medium for various time periods (24-96 h). Aorta from control rats were exposed to normal and high glucose medium for 72 h. The levels of G-proteins were determined by immunoblotting using specific antibodies. Adenylyl cyclase activity stimulated or inhibited by agonists was determined to examine the functions of G-proteins. RESULTS: The levels of Gialpha-2 and Gialpha-3 proteins in membranes from A10 cells and aorta exposed to high glucose for 3 or 4 days were significantly decreased as compared to control cells and control aorta, respectively, whereas the levels of Gsalpha protein were not altered. In addition, receptor-dependent and -independent functions of Gialpha proteins were attenuated in hyperglycemic cells, as demonstrated by inhibition of forskolin (FSK)-stimulated adenylyl cyclase activity by low concentration of GTPgammaS or by angiotensin II (Ang II), oxotremorine or C-ANP(4-23) (a ring deleted analog of atrial natriuretic peptide). On the other hand, the stimulatory effects of GTPgammaS, glucagon, isoproterenol, FSK and sodium fluoride on adenylyl cyclase were significantly augmented in hyperglycemic cells as compared to control cells, whereas basal adenylyl cyclase activity was significantly lower in hyperglycemic cells as compared to control cells. CONCLUSION: These results indicate that high glucose decreased the levels and functions of Gi proteins in A10 VSMC and aorta. It may thus be suggested that decreased levels and activity of Gi proteins and adenylyl cyclase signaling induced by hyperglycemia may be one of the important mechanisms contributing to the cardiovascular complications associated with diabetes.

Adenylyl Cyclase Inhibitors↗

PubMed2004

Hepatocyte growth factor attenuates cerebral ischemia-induced learning dysfunction.

Hepatocyte growth factor (HGF) acts as an organotropic factor for regeneration and protection in various organs and has the ability to attenuate cerebral ischemia-induced cell death. However, the effect of HGF on learning and memory function after a cerebral ischemic event is unknown. We demonstrate here that administration of human recombinant HGF (hrHGF) into the ventricle reduced the prolongation of the escape latency in the acquisition and retention tests in the water maze task on days 12-28 after microsphere embolism-induced cerebral ischemia. In addition, disruption of the blood-brain barrier at the early stage after microsphere embolism, which was determined by FITC-albumin leakage, was markedly reduced by treatment with hrHGF. We demonstrated that this effect of hrHGF on the blood-brain barrier was associated with protection against the apoptotic death of the cerebral endothelial cells at the early stage after the ischemia. These results suggest that hrHGF can prevent the learning and memory dysfunction soon after sustained cerebral ischemia by protecting against injury to the endothelial cells. The use of HGF may be a potent strategy for the treatment of cerebrovascular diseases, including cerebral infarct and vascular dementia.

Animals↗

PubMed2004

Altered Bad localization and interaction between Bad and Bcl-xL in the hippocampus after transient global ischemia.

Accumulating evidence indicates that the mitochondrial cell-death pathway, which involves the release of cytochrome c from mitochondria, participates in neuronal cell death after transient cerebral ischemia. However, the upstream events, that induce cytochrome c release after transient global ischemia are not fully understood. Bad is a pro-apoptotic member of the bcl-2 gene family that promotes apoptosis by binding to and inhibiting functions of anti-apoptotic proteins Bcl-2 and Bcl-xL. We investigated the effects of transient (15 min) global ischemia on the intracellular localization of Bad and the interaction of Bad with calcineurin, Akt or Bcl-xL in the vulnerable CA1 and resistant CA3/dentate gyrus of the hippocampus. Immunoblotting analysis revealed that the amount of Bad in mitochondria significantly increased after ischemia. Co-immunoprecipitation studies showed decreased interactions of Bad with Akt and calcineurin in the cytosol and increased binding with Bcl-xL in the mitochondrial fraction of hippocampal CA1, but not in the CA3/dentate gyrus region. Further, we examined the effect of recombinant Bad on the cytochrome c release from isolated mitochondria. Treatment with both recombinant Bad and calcium, but not with recombinant Bad alone, induced cytochrome c release. These results suggest that changes in localization and complex formation by Bad are, at least in part, involved in the vulnerability of cells after transient global ischemia.

Animals↗

PubMed2004

The effects of monobromobimane on neuronal cell death in the hippocampus after transient global cerebral ischemia in rats.

Calcium accumulation and free radical formation in the mitochondria are suggested to result in opening of the mitochondrial permeability transition pore that may be an initial step in neuronal cell death. The purpose of the present study was to determine whether monobromobimane (MBM) was a possible protective agent against neuronal cell death after transient global ischemia and the swelling of isolated hippocampal mitochondria. Infusion of MBM (1 or 3 microg) to cerebral ventricles 30 min before ischemia attenuated the expression of TUNEL-labeled cells and neuronal cell death in the hippocampal CA1 region at 72 h of reperfusion dose-dependently. Treatment with MBM inhibited an increase in caspase-3-like activity at 48 h of reperfusion in the hippocampus. MBM (30-300 microM) also inhibited an enhanced swelling rate induced by Ca2+ and phenylarsineoxide in the isolated hippocampal mitochondria. These results suggest that in vivo treatment with MBM may protect against neuronal cell death through inhibition of the mitochondrial swelling and caspase-3-dependent apoptotic pathway.

Animals↗

PubMed2004

Preservation of mitochondrial function during ischemia as a possible mechanism for cardioprotection of diltiazem against ischemia/reperfusion injury.

A possible mechanism for D-cis-diltiazem (diltiazem)-mediated improvement of the contractile function of ischemic/reperfused hearts was examined. Thirty-five-min ischemia/60-min reperfusion recovered little the left ventricular developed pressure (LVDP) and decreased myocardial high-energy phosphates (HEPs). Ischemia induced an accumulation of tissue Na+ content, an increase in cytochrome c in the cytosolic fraction, and a decrease in the oxygen consumption rate (OCR) in perfused hearts. Treatment of the heart with 1 microM diltiazem for the last 3-min of pre-ischemia did not affect the decrease in HEPs during ischemia, whereas that with 3 microM partially attenuated the decrease in ATP, suggesting that 3 microM diltiazem exerted energy-sparing effect. Treatment with 1 microM diltiazem enhanced the post-ischemic recovery of LVDP associated with attenuation of the ischemia-induced accumulation of tissue Na+, increase in cytochrome c in the cytosolic fraction, and decrease in myocardial OCR, and restoration of the myocardial HEPs during reperfusion. Combined treatment with diltiazem and a Na+/H+ exchange inhibitor, but not a Na+ channel blocker, facilitated the attenuation of Na+ accumulation in the ischemic heart and the enhancement of the post-ischemic recovery of LVDP. Sodium lactate, a possible metabolite in ischemic hearts, and sodium chloride increased the Na+ concentration in mitochondria, released cytochrome c into incubation medium, and reduced the mitochondrial respiration. Treatment of isolated mitochondria with diltiazem failed to attenuate the sodium lactate- and sodium chloride-induced alterations. These results suggest that the cardioprotection of diltiazem may be exerted via attenuating cytosolic Na+ overload through Na+ channels in the ischemic heart, leading to preservation of mitochondrial functional ability during ischemia, followed by improvement of post-ischemic energy production and contractile recovery.

Animals↗

PubMed2004

Induction of heat shock protein 72 in the failing heart is attenuated after an exposure to heat shock.

Induction of heat shock protein (Hsp) 72 in the right ventricular muscle of the rat with heart failure following acute myocardial infarction (AMI) was examined. AMI was induced by the left coronary artery ligation (CAL). The animals at the 8th, but not 2nd, week after CAL revealed a decrease in cardiac output index (COI), suggesting that heart failure had developed by 8 weeks after CAL. Increases in the right ventricular developed pressure and the ratios of right ventricle/body weight and lung/body weight at the 2nd and 8th weeks showed the development of the right ventricular hypertrophy. After measurement of hemodynamic parameters, the hearts isolated from animals at the 2nd and 8th weeks after CAL (2w- and 8w-CAL hearts, respectively) were perfused and subjected to heat shock (at 42 degrees C, for 15 min) followed by 6-h perfusion. At the end of perfusion, Hsp72 content in the left ventricle without infarct area (viable LV) and the right ventricle (RV) was determined by the Western immunoblotting method. The production of myocardial Hsp72 in the viable LV and RV of the 2w-CAL heart increased after an exposure to heat shock. In contrast, induction of Hsp72 in the viable LV and RV of the 8w-CAL heart was blunted. The results suggest that the development of heart failure following AMI may result in a decrease in the ability for Hsp72 induction not only in the viable LV but also in the RV, leading to contractile dysfunction of the heart.

Animals↗

PubMed2004

Phosphorylation of extracellular-regulating kinase in NMDA receptor antagonist-induced newly generated neurons in the adult rat dentate gyrus.

Neurogenesis in the adult brain is promoted by various stimulations. NMDA receptor blockade enhances neurogenesis in the hippocampal dentate gyrus. There is no agreed conclusion, however, as to whether newly generated neurons after NMDA receptor blockade obtain functional properties. We investigated the functional maturation of newly generated neurons after NMDA receptor blockade. In the dentate gyrus, 80% of newly generated cells differentiated into the phenotype of mature neurons at 29 days after the single intraperitoneal injection of an NMDA receptor antagonist MK-801. The number of newly generated neurons after MK-801 treatment was significantly greater than that in the saline-treated group. The neurogenic basic helix-loop-helix transcription factor NeuroD protein in the dentate gyrus after MK-801 treatment was expressed transiently in proliferative cells, but not in mature neurons. To determine functional properties of newly generated neurons, we administered NMDA to the lateral ventricle. As an in vivo response, we assessed extracellular-regulating kinase (ERK) phosphorylation. The newly generated neurons showed ERK phosphorylation by NMDA administration as seen in surrounding mature neurons. The number of newly generated neurons, which responded to NMDA receptor stimulation, increased with time after MK-801 treatment. The present study provides evidence that newly generated neurons in the adult hippocampus after NMDA receptor blockade acquire biochemical function in vivo.

Animals↗

PubMed2004

Characterization of BrdU-positive neurons induced by transient global ischemia in adult hippocampus.

Neurogenesis in the brain continues throughout life and is promoted by brain insults including ischemia. There is no critical conclusion, however, about whether proliferated cells acquire neuronal function after ischemia. Transient global ischemia was produced by a four-vessel occlusion procedure in rats (n = 54). To label proliferative cells, rats were administrated with a single dose of 5-bromo-2'-deoxyuridine (BrdU) at 4, 6, 8, 10, 13, or 15 days after ischemia. Increases in BrdU-positive cells were detected in the hippocampal dentate gyrus at 5, 7, and 9 days after ischemia. To determine the phenotype of BrdU-positive cells, BrdU was administrated twice daily for 3 consecutive days during 6 to 8 days after ischemia. A basic helix-loop-helix transcription factor NeuroD at 7 and 14 days and an immature migrating neuronal marker doublecortin at 14 days after ischemia were expressed transiently in proliferative cells. These proliferative cells after ischemia differentiated to the phenotype of neuron at 28 days after ischemia. Furthermore, BrdU-positive neurons showed phosphorylation of extracellular signal-regulated kinase (ERK) by intracerebroventricular injection of N-methyl-D-aspartate (NMDA) at 28 and 56 days after ischemia as seen in surrounding mature neurons. The number of BrdU-positive neurons, which responded to NMDA stimulation, increased with time after ischemia and was greater than that of sham-operated animals. The present study provides evidence for in vivo ERK phosphorylation in response to NMDA stimulation of BrdU-positive neurons in the adult hippocampus after transient forebrain ischemia.

Animals↗

PubMed2004

Na+ overload-induced mitochondrial damage in the ischemic heart.

Ischemia induces a decrease in myocardial contractility that may lead more or less to contractile dysfunction in the heart. When the duration of ischemia is relatively short, myocardial contractility is immediately reversed to control levels upon reperfusion. In contrast, reperfusion induces myocardial cell death when the heart is exposed to a prolonged period of ischemia. This phenomenon is the so-called "reperfusion injury". Numerous investigators have reported the mechanisms underlying myocardial reperfusion injury such as generation of free radicals, disturbance in the intracellular ion homeostasis, and lack of energy for contraction. Despite a variety of investigations concerning the mechanisms for ischemia and ischemia-reperfusion injury, ionic disturbances have been proposed to play an important role in the genesis of the ischemia-reperfusion injury. In this present study, we focused on the contribution of Na+ overload and mitochondrial dysfunction during ischemia to the genesis of this ischemia-reperfusion injury.

Animals↗

PubMed2004

Effects of monochlorobimane on cerebral ischemia-induced damage to mitochondria.

A possible involvement of inhibitory effects of monochlorobimane (MCB) on the opening of mitochondrial permeability transition (MPT) pore in the cerebroprotection against the ischemic brain injury was examined. MCB (1 mM) inhibited the opening of MPT pore in vitro. Sustained cerebral ischemia was induced by injecting 900 microspheres (48 microm in diameter) into the right hemisphere of rats. At 12 to 72 h after microsphere embolism (ME), the mitochondrial activity was determined histochemically by staining cytochrome c oxidase (COX) and succinate dehydrogenase (SDH) of the brain sections. The COX and SDH stainings in the hippocampus were observed intensively in the pyramidal neurons in the CA2-3 and dentate gyrus rather than those in the CA-1 region. The staining was decreased with time after the embolism. Pretreatment with 10 microg/animal MCB 30 min prior to the embolism significantly attenuated the ME-induced reduction in the staining of COX and SDH in the hippocampus, but not in the pariatal cortex. The results suggest that prevention of the opening of MPT pore by MCB may play an important role in the cerebroprotection against cerebral ischemic injury.

Animals↗

PubMed2004

The effects of monobromobimane on calcium and phenylarsineoxide-induced mitochondrial swelling and cytochrome C release in isolated brain mitochondria.

A possible involvement of inhibitory effects of monobromobimane (MBM), a thiol reagent, on the swelling and the release of cytochrome c in the isolated brain mitochondria was examined. MBM dose-dependently inhibited the calcium and phenylarsineoxide-induced mitochondrial swelling and cytochrome c release. Significant relationships between mitochondrial swelling and cytochrome c release were detected. Furthermore, effects of in vivo treatment with MBM on neuronal cell damage after transient (15 min) global ischemia in rats were examined. Infusion of MBM (1 or 3 microg/animal) to cerebral ventricles attenuated an increased number of TUNEL-positive cells and neuronal cell death in the hippocampal CA1 region at 72 h of reperfusion. These results suggest that MBM may have an ability to inhibit mitochondria-associated apoptotic pathways through attenuation of the mitochondrial swelling and the release of cytochrome c.

Animals↗

PubMed2004

[Induction of heat shock protein 70 in failing heart].

Heat shock protein (Hsp) 70s including Hsp72 and Hsp73 are suggested to play an important role in the cardioprotection against stress-induced functional damage. Myocardial tolerance against ischemia/reperfusion injury is increased when myocardial Hsp72 is accumulated after an exposure of normal animals to heat shock. Post-ischemic contractile recovery is improved in the perfused heart of Hsp72-overexpressed mice. However, the role of Hsp72 and Hsp73 in the failing heart following acute myocardial infarction remains unclear. The present study was undertaken to determine whether Hsp72 and Hsp73 production may contribute to the protection of cardiac function in rats with chronic heart failure (CHF) following coronary artery ligation (CAL). The rats with CAL revealed the signs of CHF at the 8th week after the operation. The hearts isolated from rats with CHF were perfused and then subjected to heat shock (at 42 degrees C) for 15 min followed by 6-h perfusion (HS group). The cardiac function of the HS group was markedly decreased and the heat shock-induced increase in myocardial Hsp72 and Hsp73 was attenuated after 6-h perfusion. In the CAL rat treated with the ACE inhibitor trandolapril from the 2nd to the 8th week, induction of Hsp70s was preserved and heat stress-induced reduction in cardiac function was attenuated. The results suggest that a reduction in the production of Hsp70s may play a significant role in the decrease in contractile function during the development of heart failure.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2003

Decrease in sarcoglycans and dystrophin in failing heart following acute myocardial infarction.

OBJECTIVE: Genetic defects in several sarcoglycans (SGs) and dystrophin (Dys) play a critical role in cardiomyopathy. The present study was designed to determine whether changes in SGs and Dys might occur in animals with chronic heart failure (CHF) induced by acute myocardial infarction (AMI), which have no genetic defects. METHODS: AMI was induced by the left coronary artery ligation (CAL) in rats. The hemodynamic parameters of the 2- and 8-week CAL (2w- and 8w-CAL) rats were measured and the myocardial SGs, Dys, calpain, and calpastatin levels were determined by the Western blot method. Myocardial calpain-like protease activity was evaluated as caseinolysis activity. RESULTS: Increases in left ventricular end-diastolic pressure (LVEDP) and right ventricular systolic pressure, and a decrease in +/-dP/dt were observed at the 2nd week, whereas cardiac output index (COI) was preserved. In contrast, the 8w-CAL rats showed a further increment in LVEDP with low COI. alpha-SG of the viable left ventricle (LV), and septum (Sep) of the 8w-CAL rat decreased (60-70% of the control). The alpha- and beta-SGs of the right ventricle (RV) of the 2w- and 8w-CAL rats were reduced, while gamma- and delta-SGs in the three regions did not change significantly. Dys in the viable LV and RV of the 8w-CAL rat decreased (75% of the control). The amount of m-calpain in the three regions of the 2w- and 8w-CAL rats increased (140-200% of the control), whereas the endogenous calpain inhibitor, calpastatin, did not change significantly. The in vitro degradation studies using purified m-calpain or cytosolic fractions of the 8w-CAL rat heart suggested a reduction in SGs and Dys by calpain. CONCLUSION: The results suggest that a decrease in SGs and Dys may play an important role in the pathophysiology of CHF following AMI.

Animals↗

PubMed2003

Rapid appearance of pathological changes of neurons and glia cells in the cerebellum of microsphere-embolized rats.

Neuropathological changes in the cerebellar cortex of microsphere-embolized rats were studied at 30 min and 3 h after the embolism. Necrotic processes including a sponge-like vacuolation in the molecular layer, a vague outline of some Purkinje cells, and a few pyknotic granule cells having small and dark profiles were identified at sometime between 30 min and 3 h after microsphere-induced embolism in Nissl staining. Glial fibrillary acidic protein staining shows an apparent reduction in the number of Bergmann glial processes in some of the areas where there was necrosis of the molecular layer and poor astroglia processes in the areas subjacent to the pyknotic granule cells. These data demonstrate that within a short time, microsphere-induced cerebral ischemia produces necrosis of cerebellar neurons (i.e. Purkinje and granule cells) and changes in cerebellar glia cells (i.e. Bergmann and astroglia cells), and that these neuropathological changes are secondary phenomenon caused by microsphere blockage of cerebellar blood flow.

Animals↗