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S Z Lin

Publications and source records attributed to S Z Lin.

At least 19 recordsLinked to original sources
PubMed1999

Osteogenic protein-1 protects against cerebral infarction induced by MCA ligation in adult rats.

BACKGROUND AND PURPOSE: Osteogenic protein-1 (OP1) not only possesses trophic activity on bone tissue but also influences neuronal survival and differentiation in vitro. Specific receptors for OP1 are present in brain and spinal cord and can be upregulated during cerebral contusion. OP1 is a member of the transforming growth factor-beta superfamily, several of whose members possess neuroprotective activity. In this study, the neuroprotective effect of OP1 in cerebral ischemia was evaluated in adult animals. METHODS: Adult male Sprague-Dawley rats were anesthetized with chloral hydrate. OP1 or vehicle was administered intracortically or intracerebroventricularly to the rats. Thirty minutes, 24 hours, or 72 hours after OP1 injection, the right middle cerebral artery (MCA) was ligated for 90 minutes. Twenty-four hours after reperfusion, animals were tested for motor behavior. The animals were subsequently anesthetized with urethane and perfused intracardially with saline. Brain tissue was removed, sliced, and incubated with 2% triphenyltetrazolium chloride to localize the area of infarction. RESULTS: Only animals pretreated with OP1 24 hours before MCA ligation showed a reduction in motor impairment. OP1, given 30 minutes or 72 hours before MCA ligation, did not reduce cortical infarction. In contrast, pretreatment with OP1 24 hours before MCA ligation significantly attenuated the volume of infarction in the cortex, in agreement with the behavioral findings. CONCLUSIONS: Intracerebral administration of OP1 24 hours before MCA ligation reduces ischemia-induced injury in the cerebral cortex.

Animals↗
PubMed1998

The effect of trigeminal neurotomy on the alteration of local cerebral blood flow of normotensive and hypertensive rats in acute cold stress.

The cold season is reported to have the highest incidence of stroke in a year. Cold is usually detected by cold receptors in the face. The present studies were designed to test whether the trigeminal nerve plays a role in the regulation of local cerebral blood flow (LCBF) in animals exposed to a cold environment. Since hypertension affects the incidence of strokes, both Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were used. Each species was divided into four groups: trigeminal neurotomy (TNx) or control group at room temperature (20 degrees C) or cold environment (5 degrees C), respectively. LCBF in 14 brain structures was measured using the [14C] iodoantipyrine technique and tissue dissecting methods. Our results show that TNx did not alter physiological parameters and LCBFs in WKY and SHR kept either at 20 degrees C or at 5 degrees C for 30 min. However, a transient exposure (30 minutes) to cold caused concomitantly a significant decrease in core body temperature of both WKY and SHR groups (p<0.05, Student's paired t-test) and a significant decrease in LCBFs at the temporal cortex (TC), hypothalamus (HYP) and midbrain (MID) of WKY and TC of SHR (P<0.05, MANOVA). TNx did not alter LCBFs significantly following transient cold exposure in WKY and SHR. Our findings indicate that in the cold environment, the lowered LCBFs in some areas of the brain may relate to the decreased metabolic rate caused by decreased body temperature, and may partly contribute to the higher prevalence of stroke in winter. Our findings also suggest that trigeminal nerve do not exert tonic control of LCBFs and the cold afferents in trigeminal nerve are not important in modulation of the LCBFs.

Animals↗
PubMed1998

Inorganic Pi increases neuronal survival in the acute early phase following excitotoxic/oxidative insults.

Inorganic phosphate (Pi) plays a vital role in intracellular energy metabolism. Its many effects include stimulation of glucose use, enhancement of high-energy phosphate concentrations, and modulation of cytosolic free [Ca2+]. Cultured fetal rat cortical neurons constitutively import Pi, and cytosolic levels positively correlate with [ATP], [NADPH], and energy charge. In the present study, we demonstrate that the concentration of intracellular Pi is an important determinant of acute neuronal survival after an excitotoxic or oxidative insult to cultured fetal rat cortical neurons. Extracellular Pi dose-dependently enhanced survival of cortical neurons after exposure to NMDA at early (< or = 6 h) time points after termination of the insult. Pi similarly increased neuronal survival after exposure to kainic acid or H2O2. Pi-exposed neurons had higher basal intracellular [Pi], [ATP], and [GSH], and slightly lower cytosolic free [Ca2+], compared with Pi-deprived neurons. Pi-exposed neurons maintained increased [ATP] after exposure to NMDA and displayed reduced formation of reactive oxygen species after exposure to kainic acid or H2O2, compared with Pi-deprived neurons. These findings demonstrate that changes in extracellular and intracellular Pi can affect neuronal survival after excitotoxic or oxidative insults.

Animals↗
PubMed1998

The effect of sphenopalatine postganglionic neurotomy on the alteration of local cerebral blood flow of normotensive and hypertensive rats in acute cold stress.

The cold season of a year has been reported to have the highest incidence of strokes. Present studies were designed to test whether the parasympathetic denervation plays any role in the regulation of local cerebral blood flow (LCBF) in anesthetized animals exposed to a cold environment. Each species of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) was divided into four groups: sphenopalatine postganglionic neurotomy (SPNx) or a control group at room temperature (20 degrees C) or in a cold environment (5 degrees C), respectively. LCBF in 14 brain structures was measured using the [14C] iodoantipyrine technique and tissue dissecting methods. Our results show that SPNx did not significantly alter physiological parameters and LCBF in WKY and SHR kept at either 20 degrees C or 5 degrees C. However, 30 minutes of cold exposure caused a significant decrease in the core body temperature of both the WKY and SHR groups (P < 0.05, Student's paired t-test) and a significant decrease in LCBF in 3 of 14 brain areas: the temporal cortex (TC), inferior colliculus (IC) and vermis (VER) of both WKY and SHR (P < 0.05, MANOVA). The percentages of decrease were 24% (TC), 12% (IC), 12% (VER) and 19% (TC), 16% (IC), 15% (VER), respectively. Our findings indicate that in a cold environment, the lower LCBFs in some areas of the brain may be related to decreased body temperature. Whether they are related to the higher prevalence of stroke in winter needs further investigation.

Animals↗
PubMed1997

Mastoparan-induced apoptosis of cultured cerebellar granule neurons is initiated by calcium release from intracellular stores.

We have recently reported that mastoparan, a peptide toxin isolated from wasp venom, induces apoptosis in cultured cerebellar granule neurons that can be blocked by cholera toxin, an activator of Gs. Measurements of intracellular free calcium concentration ([Ca2+]i) reveal that mastoparan induces a dramatic elevation of [Ca2+]i that is frequently followed by enhanced leakage of fura-2 out of the neurons, suggesting that this rise in [Ca2+]i may be due to a more generalized change in membrane permeability. However, the mastoparan-induced initial elevation of [Ca2+]i is maintained in the absence of extracellular Ca2+, suggesting that the rise of [Ca2+]i is from intracellular stores. This conclusion is supported by the observation that depletion of [Ca2+]i stores by pretreatment with either caffeine or thapsigargin attenuates both the rise in [Ca2+]i and cell death induced by mastoparan. Phospholipase C (PLC) inhibitors, neomycin and U73122 block mastoparan-induced increases of [Ca2+]i and protect against neuronal death. Pretreatment with cholera toxin, but not pertussis toxin, reduced the mastoparan-induced rise in [Ca2+]i. Taken together, our data suggest that mastoparan initiates cell death in cerebellar granule neurons by inducing Ca2+ release from intracellular stores, probably via activation of PLC and IP3. A secondary or parallel process results in disruption of plasma membrane integrity and may be ultimately responsible for the death of these neurons by mastoparan.

Animals↗
PubMed1997

Transplantation of microencapsulated PC12 cells provides long-term improvement of dopaminergic functions.

The purpose of this study is to examine if microencapsulated PC12 cells may provide long term effects to the hemiparkinsonian rats. A modified technique was used to encapsulate PC12 cells into gelled microspheres. We found that the PC12 cells can survive in the modified microcapsules in vitro. Most of the PC12 cells formed cluster 3 weeks after incubation. The PC12 cell-loaded microcapsules were also examined in vitro. Adult Sprague-Dawley rats, anesthetized with chloral hydrate, were injected unilaterally with 6-hydroxydopamine into the medial forebrain bundle. The effectiveness of this lesion was tested by measuring apomorphine or methamphetamine-induced rotation one month after lesioning. The unilaterally lesioned rats were transplanted with microencapsulated PC12 cells. Results showed that apomorphine and methamphetamine-induced rotations were greatly suppressed after transplantation. One year after the grafting, the animals were anesthetized with urethane for the voltammetric study. Low dose of KCl was directly injected into the grafted striatum through pressure microejection. We found that KCl-induced DA release, as measured by voltammetric techniques, was regenerated in the striatum. The animals were later sacrificed for histological examination. We found that capsules were present in the lesioned striatum one year after grafting. Most of the capsules contained no PC12 cell. However, some capsules were filled entirely with PC12 cells. Taken together, our data suggested that PC12 cells can survive in the capsule in vitro and may provide long-term dopaminergic effects to the hemiparkinsonian rats.

Animals↗
PubMed1997

Glial cell line-derived neurotrophic factor protects against ischemia-induced injury in the cerebral cortex.

Glial cell line-derived neurotrophic factor (GDNF), a recently described and cloned member of the transforming growth factor (TGF)-beta superfamily, has been shown to have marked trophic activity on several populations of central neurons. Survival-promoting and injury protectant activity in vitro and in vivo, using several paradigms, has been demonstrated for ventral mesencephalic dopaminergic neurons and spinal cord motoneurons. In view of a proposed commonality of mechanisms, involving intracellular free radical generation, depolarization-induced Ca2+ influx, and mitochondrial respiratory enzyme injury, between such GDNF-responsive paradigms and those of ischemia-induced injury, we tested the effects of GDNF on the extent of neural degeneration induced by transient middle cerebral artery (MCA) occlusion. We now report that intracerebroventricular and intraparenchymal administration of GDNF potently protects the cerebral hemispheres from damage induced by MCA occlusion. In addition, the increase in nitric oxide that accompanies MCA occlusion and subsequent reperfusion is blocked almost completely by GDNF. Thus, this protein may play an important role in the treatment of cerebrovascular occlusive disease.

Age Factors↗
PubMed1997

Evaluation of recombinant chitinase and SXP1 antigens as antimicrofilarial vaccines.

Prior studies indicate that a microfilarial stage-specific chitinase is a possible candidate antigen for a transmission-blocking vaccine against Brugian filariasis. The antigen is a functional enzyme that progressively appears as microfilariae mature and become able to infect and develop in a susceptible mosquito vector. It is recognized by a monoclonal antibody that reduces microfilaremia in infected animals and by a subset of sera from infected persons who remain amicrofilaremic. Immunization of jirds with recombinant chitinase induced partial protection against microfilaremia resulting from subsequent infection with Brugia malayi, but did not reduce adult worm burdens. Vaccination was much less effective when administered during the prepatent stage of infection and was ineffective when given to microfilaremic jirds. The protective epitope appears to be located close to the carboxy terminus of the chitinase molecule. Immunization of jirds with SXP1, an antigen present in multiple worm stages, also reduced microfilaremia and, in some experiments, adult worm burdens, but hyperimmunization with a recombinant filarial myosin was not protective. These observations indicate that the relative timing of immunization and infection is an important factor in the efficacy of antimicrofilarial vaccines.

Animals↗
PubMed1996

Pineal ganglioglioma with premature thelarche. Report of a case and review of the literature.

We report a case of a 6-year-old girl with a ganglioglioma in the pineal region presenting with a rare clinical picture of premature thelarche. Intracranial gangliogliomas are rare, especially in the pineal region. Their character, origin, treatment, and prognosis remain controversial. The pathophysiology of precocious puberty associated with pineal ganglioglioma is discussed.

Brain Neoplasms↗
PubMed1996

Isovolemic hemodilution normalizes the prolonged passage of red cells and plasma through cerebral microvessels in the partially ischemic forebrain of rats.

The objective of this study was to determine whether hemodilution could normalize the mean transit times of red blood cells (Tr) and plasma (Tp) through cerebral microvessels in a partially ischemic brain. Wistar-Kyoto (WKY) rats, aged 30-40 weeks, were divided randomly into three groups. The first group was the nonocclusion, nonhemodilution (NN) normal control group. The second group was the occlusion, nonhemodilution (ON) group, in which animals were treated with bilateral carotid artery ligation. The third group was the occlusion-hemodilution (OH) group, in which animals were treated with bilateral common carotid artery ligation and, then, isovolemic hemodilution by replacing blood with the same volume of 3% modified fluid gelatin. Local cerebral blood flow (lCBF) and microvascular volumes of red blood cells (Vr) and plasma (Vp) in 14 brain structures were measured using 14C-iodoantipyrine, iron-55 labeled red blood cells, and 14C-inulin, respectively. The amount of oxygen delivered to local brain structures (OD), cerebral microvascular blood volume (Vb), mean transit time of blood (Tb), Tr, and Tp through cerebral microvessels were calculated from the data. Two hours after carotid artery ligation, lCBF decreased by approximately 38% in forebrain structures, 22% in rostral hindbrain areas, and 8% in the caudal hindbrain (29% for all 14 structures). The decreases in ODs were parallel with those of lCBFs, at 33, 17, and 2% in the three regions, respectively (24% for all structures). In contrast, Vb increased by 68, 37, and 16% in the three regions, respectively (48% for all structures). Tr and Tp were markedly prolonged (180% for Tr and 154% for Tp) in the forebrain regions, moderately (91% for Tr and 73% for Tp) in the rostral hindbrain, and mildly (60% for Tr and 13% for Tp) in the caudal hindbrain, with a mean increase of 136% for Tr and 111% for Tp in all structures. When data in the OH and NN groups were compared, lCBF values tended to be slightly higher and Vb values were significantly higher (p < 0.05) in the OH group. ODs in the eight forebrain structures were all significantly less (p < 0.05) in the OH group than the NN group. Tr and Tp values in the forebrain were similar between the OH and the NN groups. In conclusion, occlusion of the bilateral common carotid arteries in WKY rats causes partial forebrain ischemia, in which both Tr and Tp are prolonged. These prolongations of Tr and Tp can be normalized by isovolemic hemodilution. However, the ischemic forebrain remains hypoxic after hemodilution.

Animals↗
PubMed1996

Ketamine antagonizes nitric oxide release from cerebral cortex after middle cerebral artery ligation in rats.

BACKGROUND AND PURPOSE: Ischemia or hypoxia activates N-methyl-D-aspartate (NMDA) receptors and results in nitric oxide (NO) production. The purpose of this study was to investigate whether an NMDA channel blocker can inhibit NO production during ischemia. METHODS: Temporary cerebral ischemia was induced by middle cerebral artery ligation while common carotid arteries were clamped bilaterally for 40 minutes in urethane-anesthetized rats. Extracellular NO concentration in the cortex was recorded through Nafion- and porphyrine-coated carbon fiber electrodes. Ketamine, and NMDA channel blocker, was administered (50 mg/kg) intraperitoneally 15 minutes before the cerebral artery ligation. RESULTS: During middle cerebral artery ligation, cortical NO was increased to its peak (18.76+/-3.36 nmol/L) in 7 minutes and then declined. The overflow of NO can be antagonized by pretreatment with ketamine, dizocilpine maleate (MK801), or N(G)-nitro-L-arginine methyl ester (L-NAME). Local application of nitroprusside also induced NO production. However, this effect was not antagonized by ketamine. CONCLUSIONS: These findings demonstrated that NO release induced by short-term cerebral ischemia can be attenuated by pretreatment with NMDA antagonists.

Animals↗
PubMed1996

Characterization of steroid/cyclodextrin inclusion compounds by x-ray powder diffractometry and thermal analysis.

Two inclusion compounds, progesterone with beta- and gamma-cyclodextrin, were studied with X-ray powder diffractometry and thermal analysis. Disappearance of characteristic X-ray diffraction patterns of the two compounds as well as the appearance of a new diffraction pattern for each were found when formation of the inclusion compounds was completed. The X-ray diffraction patterns of beta-cyclodextrin measured at various temperatures showed a structural change occurring between 60 degrees C to 80 degrees C, which coincided well with the DSC endothermic peak around 75 degrees C. Results suggest that changes in the X-ray diffraction patterns of cyclodextrin during inclusion formation and during heating is due to the displacement of adsorbed water by progesterone in the cavity of cyclodextrin.

Crystallography, X-Ray↗
PubMed1996

Alteration of cerebral microcirculation by hemodilution with hemosome in awake rats.

Our study showed that hemodilution with modified fluid gelatin resulted in an increase in local cerebral blood flow (LCBF), but no change at all in local cerebral oxygen delivery (LCOD) in rats. Hemosome, a lecithin encapsulated hemoglobin having the oxygen-carrying capacity, was developed to improve LCOD by hemodilution. Therefore, we have hypothesized that LCBF & LCOD would be increased by hemodilution with hemosome. To test this hypothesis, adult male Sprague-Dawley rats weighing approximately 350g were used and divided into the hemodilution and the control groups. Hemosome was made from pig red blood cells and lecithin. It's mean diameter was approximately 0.3 um and hemoglobin concentration was approximately 4g/dl. Isovolemic hemodilution, which lowered the systemic hematocrit from approximately 50% to approximately 30%, was achieved by rapidly replacing blood with the same volume of hemosome. Ten min later, LCBF in 14 brain structures were measured using the 14C-iodoantipyrine technique. Our results showed that LCBF of the control group ranged from 115 +/- 11 ml/100g/min in the medulla to 260 +/- 31 ml/100g/min in the occipital cortex. LCBFs were generally higher (p < 0.05, MANOVA) by 16% in the hemodilution group than in the control group. However LCODs were generally decreased (p < 0.05, MANOVA) by 18% in the hemodilution group than in the control. In conclusion, hemodilution with hemosome indeed improves LCBF but lowers LCOD in awake rats.

Analysis of Variance↗
PubMed1995

Differential regulation of cyclin A, cyclin B and p21 concentrations in a growth-restricted human fibroblast cell line.

When the culture temperature was shifted from 35 degrees C to 39 degrees C, human fibroblasts immortalized by the temperature-sensitive simian virus 40 T antigen became larger and acquired the morphological characteristics of senescent fibroblasts. After culture at 39 degrees C for 48 h, most cells had ceased to proliferate. A rapid depletion of cells with S-phase DNA content was observed after the temperature shift. To elucidate the mechanism governing this rapid arrest of proliferation, we studied the expression of genes involved in the regulation of cell cycle progression. Cyclin A, cyclin B and p34cdc2 concentrations were not changed during growth restriction, whereas p21 was rapidly induced in these growth-restricted cells. Transient expression of exogenous p21 in cells cultured at 35 degrees C led to growth restriction and morphological changes characteristic of senescence. Furthermore, we studied the reversibility of growth restriction induced by the temperature increase. The results showed that senescent morphology and growth arrest were not reversible. In these cells the p21 concentration remained high and p34cdc2 remained undetectable. This indicates that p21 accumulation might be responsible for the maintenance of senescence. Our findings provide information on the use of growth restriction of immortalized fibroblasts induced by a temperature shift as a model system to study senescence.

CDC2 Protein Kinase↗
PubMed1995

Regional skin blood flow in deep burn wounds: a preliminary report.

Local skin blood flow (LSBF) using the Walker's deep burn rat model was studied on the first three postburn days using the carbon-14 iodoantipyrine ([14C]IAP) perfusion method. The radioactive [14C]IAP (12.5 microCi) was infused through the femoral vein over a period of 30 seconds and the blood samples were collected by a free flow from the femoral artery at 5-s intervals to evaluate the concentration of the isotope, in the blood. At the conclusion of the infusion, the rats were guillotined and biopsies were obtained from the burned skin, unburned skin from burned rats and skin from sham control rats to assay the isotope in the skin. The LSBF was calculated from the skin tissue and plasma radioactivity data using Jay's equation. The results showed significant decreases of the skin blood flow in the deep burn wound with 4.05 +/- 1.16, 5.31 +/- 1.32 and 4.77 +/- 2.48 ml/100 g/min as compared to the LSBF of unburned skin 10.27 +/- 1.49, 12.39 +/- 2.05, 14.79 +/- 1.85 ml/100 g/min on postburn days 1, 2 and 3 (P < 0.05). The blood flow of the control group skin was 11.5 +/- 1.97 ml/100 g/min (P < 0.05). There were also significant differences of LSBF among burn wounds on postburn days 1, 2 and 3 (P < 0.05). Pathological study of the deep burn wound showed that more of the blood flow was in the subcutaneous adjacent areolar tissue, than in the deep reticular dermis, and only a little occurred in the upper reticular dermis occasionally.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Characterization of the excitoprotective actions of N-methyl-D-aspartate in cultured cerebellar granule neurons.

Exposure of cultured cerebellar granule neurons to subtoxic concentrations of N-methyl-D-aspartate (NMDA) has been shown previously to result in a neuroprotective state, as measured by subsequent exposure to toxic concentrations of glutamate. In the present study, we have further characterized the excitoprotective actions of NMDA in these neurons. NMDA-induced excitoprotection was concentration dependent (EC50 approximately 30 microM) and time dependent, with maximal protection observed following 16 h of preexposure to NMDA. NMDA-induced excitoprotection did not require continuous exposure to NMDA, as a 4-h preincubation was sufficient to induce full excitoprotection when measured 8 h later. Maximal protection was manifest as a "right shift" in the concentration-response relationship for glutamate toxicity of approximately three orders of magnitude (EC50 approximately 30 microM in untreated neurons compared with > or = 50 mM in NMDA-treated neurons). After removal of NMDA, complete reversal of the excitoprotective state was observed by 48 h (t1/2 approximately 24 h). The ability of NMDA to induce excitoprotection was observed in neurons maintained for up to 14 days in vitro (DIV) [postnatal day (PND) 22], but was absent at 21 and 32 DIV (PND 29-40), despite little to no difference in the toxicity of glutamate at any DIV examined. Preexposure of cerebellar granule neurons to a maximally excitoprotective concentration of NMDA (50 microM) failed to alter the density of NMDA receptors measured by the specific binding of [3H]MK-801.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗