Spacial and temporal profiles of neutrophil accumulation in the reperfused ischemic myocardium

To elucidate further the pathogenic role of neutrophils in evolving reperfused myocardial infarction, we investigated the dynamics of their accumulation and distribution in the ischemic myocardium. The left anterior descending coronary artery was occluded in dogs for 2 hours followed by reperfusion for 0, 3, 6, or 24 hours. 111In-labeled neutrophils were injected at the time of occlusion or after 16 hours of reperfusion. The area at risk was similar among groups. Infarct size expressed in percent of the area at risk was identical between groups reperfused for 6 (35.2 +/- 4.4%) or 24 (32.3 +/- 3.9%) hours but smaller (22.0 +/- 4.4%; p less than 0.05) after 3 hours of reperfusion. 111In-neutrophils accumulation quantified by scintigraphy correlated positively with infarct size (r = 0.64, p less than 0.005); accumulation rates (cells/h/cm2MI) were high during the first 3 (2288 +/- 754) and 6 hours (1953 +/- 463) but low (490 +/- 192) between 16 and 24 hours of reperfusion. Cells accumulating during reperfusion (12,566 +/- 2307 cells/g at 3 hours) were found within the borders of the necrotic area, and the cell counts (2420 +/- 724 cells/g, p less than 0.05) in the live tissue located within the area at risk after 3 hours of reperfusion were similar to those found in the subepicardium at the onset of reperfusion: (2240 +/- 571 cells/g). Only a few cells were detected in the normally perfused myocardium (67 +/- 33 cells/g). We conclude that reperfusion accumulation in the ischemic myocardium; the reaction takes place within 3-6 hours of reperfusion, a period of time where infarct size is growing by about 40%. These results support the concept that leukocytes may play a pathogenic role on infarct size in models with brief ischemia followed by reperfusion.     

Light and electron microscopic study of the degeneration and early regeneration of olfactory epithelium in the mouse

Degeneration and early regeneration of olfactory epithelium from two strains of mice was studied at the light and electron microscopic levels from 12 hours to 3 days following nasal irrigation with 1% aqueous solution of zinc sulfate (ZnSO₄) (a compound known to selectively damage olfactory epithelium). Distinct patterns of degeneration and stages of regeneration were evident following treatment. During the first 24 hours after treatment three progressive manifestations of the degenerative process were seen: (1) a relatively mild condition which was characterized by surface irregularities produced by cell protrusions, highly vacuolated cytoplasm, presence of large lysosome-like bodies and prominent intercellular spaces, (2) a more severe condition in which large areas of the epithelium were detached from the basement membrane and cellular debris was present in the nasal chamber, and (3) a condition of total or near-total denudation of the epithelium of olfactory mucosa. The basal lamina was continuous and intact in most regions and the integrity of the subjacent connective tissue was mostly well-preserved. Nerve bundles of the fila olfactoria were noted in varying degrees of degeneration during the course of the experiment. The most advanced neural degeneration was seen 24 to 72 hours after treatment. Onset of regeneration was suggested by the appearance of a simple squamous layer of cells above the basement membrane 48 to 72 hours after treatment. In addition to the simple epithelium a stratified epithelium consisting of two to four cell layers was also observed at this time. Glandular cells, containing secretory granules identical to those in Bowman's glandular cells, were noted in an apparent process of migration from the lamina propria into the stratified epithelial layer. The last mentioned observation supports the proposition that new supportive epithelial cells originate from cells of Bowman's gland.     

Histopathological findings in rabbits after experimental acute exposure to the Loxosceles intermedia (brown spider) venom

Loxoscelism, the term used to describe envenomation with brown spiders, is characterized by a dermonecrotic lesion at the bite site. In the present investigation we submitted albino rabbits to an acute experimental envenomation protocol using Loxosceles intermedia (brown spider) venom, with in order to determine the pathogenesic features of the lesion induced by this spider, which is the cause of several accidents throughout the world. Rabbits received intradermal injections of the venom and were monitored over the first 4 h, and then at 12 h and 1, 2 and 5 days after envenomation. Histological specimens from 3 rabbits per time point were collected from euthanized animals and processed for histological examination by light microscopy. Major findings observed during the first 4 h were oedema, haemorrhage, degeneration of blood vessel walls, plasma exudation, thrombosis, neutrophil accumulation in and around blood vessels with an intensive diapedesis, a diffuse collection of inflammatory cells (polymorphonuclear leucocytes) in the dermis, and subcutaneous muscular oedema. Over the following hours and up to 5 days after envenomation the changes progressed to massive neutrophil infiltration (with no other leucocytes) into the dermis and even into subcutaneous muscle tissue, destruction of blood vessels, thrombosis, haemorrhage, myonecrosis, and coagulative necrosis on the 5th day.     

Rat pulmonary artery restructuring and pulmonary hypertension induced by continuous Escherichia coli endotoxin infusion

We have studied the effect of continuous endotoxin infusion on rat pulmonary structure and function (69.4 ng/100 gm body weight/min for 24 hours). After 6 days of endotoxin infusion, lack of filling of pre- and intraacinar arteries was evident on pulmonary arteriograms. Microscopy demonstrated lumen narrowing in preacinar arteries and occlusion of intraacinar arteries. Morphometry of patent intraacinar arteries established dilation and increased wall muscle. Widespread alveolar wall injury was evident. After 24 hours of infusion, pulmonary artery pressure was raised (delta 9 mmHg; p less than or equal to 0.001); it then fell but was again increased by day 6 (delta 6 mmHg; p less than or equal to 0.05). Pulmonary vascular resistance was markedly increased at 24 hours (day 0 = 0.1 +/- 0.011 dyne/sec/cm-5; 24 hours endotoxin = 0.572 +/- 0.102 dyne/sec/cm-5; p less than or equal to 0.02). It remained elevated during the infusion period but was not significant. At day 6 the alveolar-arterial oxygen diffusion gradient (A-aDO2) was increased (day 0 = 19.6 +/- 1.39 mmHg, day 6 endotoxin = 33.8 +/- 0.1 mmHg; p less than or equal to 0.001). The arterial oxygen tension (PaO2) was decreased (day 0 = 86.5 +/- 1.8 mmHg, day 6 endotoxin = 74 +/- 2.52 mmHg; p less than or equal to 0.05), as was the arterial carbon dioxide tension (PaCO2) (day 0 = 36.0 +/- 0.73 mmHg, day 6 endotoxin = 30 +/- 1.9 mmHg; p less than or equal to 0.05). Thrombocytopenia occurred during the first 72 hours of infusion (day 0 = 7.41 +/- 0.41 X 10(5)/mm3, day 1 endotoxin = 2.43 +/- 0.30 X 10(5)/mm3, day 3 endotoxin = 2.32 +/- 0.31 X 10(5)/mm3; p less than or equal to 0.001) but by day 6 the platelet count had returned to basal levels (9.9 +/- 0.65 X 10(5)/mm3). Endotoxin increased the number of leukocytes in peripheral blood (day 0 = 12.8 +/- 1.2 X 10(3)/mm3, day 3 endotoxin = 17.0 +/- 1.86 X 10(3)/mm3, day 6 endotoxin = 22.5 +/- 1.8 X 10(3)/mm3; p less than or equal to 0.01 for day 6). Plasma concentrations of 6-keto-prostaglandin F1 alpha decreased during the first 24 hours of infusion (day 0 = 0.56 +/- 0.076 ng/ml, 24 hours endotoxin = 0.27 +/- 0.026 ng/ml; p less than or equal to 0.05) and thromboxane (TX) B2 in the first 15 hours (day 0 = 0.23 +/- 0.058 ng/ml, 15 hours endotoxin = 0.09 +/- 0.14 ng/ml; p less than or equal to 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)     

Localization of inducible nitric oxide synthase to mast cells during ischemia/reperfusion injury of skeletal muscle

Nitric oxide contributes to tissue necrosis after ischemia-reperfusion (IR). A biochemical and immunohistochemical study was made of the amounts and localization of both Ca++-independent nitric oxide synthase (NOS) II and Ca++-dependent (NOS I and NOS III) in rat skeletal muscle after ischemia and 0.5, 2, 8, 16, and 24 hours reperfusion. NOS II was not detectable in control muscle or during ischemia, was first detected after 2 hours reperfusion, increased further by 8 hours, and remained elevated at 24 hours. Both NOS II and nitrotyrosine, a marker of peroxynitrite formation, were localized exclusively to mast cells except after 24 hours reperfusion when some macrophages and neutrophils also showed positive immunoreactivity. Mast cells underwent extensive degranulation during reperfusion. NOS I was not detected in injured or control muscle. The level of NOS III, which was localized to the endothelium of blood vessels of all sizes in control muscle, decreased progressively during ischemia and reperfusion to reach undetectable levels after 16 hours reperfusion. These findings indicate that most of the nitric oxide formed during IR injury is generated by NOS II located almost exclusively in mast cells.     

Response of circadian locomotor activity and the proestrous luteinizing hormone surge to phase shifts of the light-dark cycle in the hamster

Female hamsters with regular 4 day estrous cycles were exposed to either a 3 hour phase advance or delay of the 14:10 light-dark (LD) cycle on the first, second or third day before proestrus. Blood samples were taken on proestrus to characterize the LH surge, and locomotor activity onset was recorded. Both the LH surge and activity onset phase delayed more quickly than they advanced, which can be explained by the free-running period of the hamster (longer than 24 hours). Higher estradiol levels were correlated with more rapid advances of activity onset.     

Morphological estimation of brain extracellular fluid dynamics in cold-induced edema from the aspect of cerebrospinal fluid-extracellular fluid communication

Following the induction of cold injury in the parietal cortex of rats, the brain extracellular fluid dynamics under conditions of cryogenic edema were investigated morphologically from the aspect of extracellular fluid (ECF)-cerebrospinal fluid (CSF) communication using horseradish peroxidase (HRP) injected into the cisterna magna as a marker. About 24 h after the induction of cold injury, HRP was distributed in the subjacent white matter of the lesion and around the ventricle. Forty-eight hours after injury, the distribution of HRP around the lesion became distinctive. This distribution of HRP became more concentrated at the same location on day 3-4 after injury. At this time, HRP was observed to be distributed along the walls of small vessels, in the cytoplasm of a few neurons and in the neuropil around the lesion by light microscopy. At small vessels around the lesion, a dense deposit of HRP at the basement membrane and many abluminal vesicles were evident by electron microscopy. These findings indicate that ECF-CSF communication changes drastically under the influence of edema fluid dynamics. In particular, the dense distribution of HRP around the lesion on day 3-4 after injury can be attributed to active retrograde transport by vessels in this area, a phenomenon considered important for edema resolution.     

Vascularization of normal and neoplastic tissues grafted to the chick chorioallantois. Role of host and preexisting graft blood vessels.

Adult, embryonic, and tumor tissues were grafted to the chorioallantoic membrane of the chick embryo to determine whether blood vessels originally within implants were reused in the establishment of a new blood supply. Grafts were examined daily by in vivo stereomicroscopy and in histologic sections. Colloidal carbon injections into the host vasculature served to confirm the precise onset of graft circulation; Preexisting tumor blood vessels disintegrated by 24 hours after implantation and revascularization occurred at 3 days by penetration of proliferating host vessels into the tumor tissue. Adult tissues did not revascularize, and the original graft vasculature progressively disintegrated during the 9 days of observation, Most embryonic tissues revascularized in 1 or 2 days by reperfusion of the existing graft vasculature. Anastomosis of host and graft blood vessels seemed to result from connections between newly formed vascular sprouts arising from both vasculatures. This study indicates that only tumor grafts acquire their blood supply solely by formation of new blood vessels from the host microvasculature. By contrast revascularization of normal tissues, when it does occur, is predominately the result of perfusion of the preexisting graft blood vessels.     

Mechanism of deletion of endothelial cells during regression of the corpus luteum

Endothelial cells are deleted rapidly, and in large numbers, during cyclical regression of the corpus luteum of the guinea pig. This paper reports a study of the mechanisms, structural and causal, by which this deletion occurs. Corpora lutea from guinea pigs were examined by transmission electron microscopy on day 9 (functional stage) and day 16 (regressing) of the estrous cycle. Corpora lutea were also studied at 1, 3, 12, 24, and 48 hours after administration of a synthetic luteolytic substance (cloprostenol), and after temporary occlusion of the ovarian blood vessels for 15, 30, 60, or 120 minutes. Early signs of endothelial cell degeneration included protrusion of some individual cells into capillary lumina and the formation of adherens junctions across the lumen. Intermediate stages of degeneration included nuclear and cytoplasmic condensation and cellular and nuclear lobation or fragmentation in cells either protruding into, or lying within, the lumen. Terminal changes included loss of plasma membrane integrity and cytoplasmic density, together with disruption of cell organelles. Some degenerate endothelial cells were engulfed by viable endothelial cells. Macrophages were not seen to be involved in removal of dead endothelial cells, and integrity of the walls of capillaries was maintained while individual endothelial cells were deleted. Experimental findings were consistent with the hypothesis that cessation or reduction of flow of blood along capillaries plays an etiologic rule in endothelial cell deletion.     

Early and late pathologic changes in the adrenal glands of mice after infection with herpes simplex virus type 1

Intranasal infection of CH/HeN mice with herpes simplex virus Type 1 (HSV-1), VR3 strain, caused a high death rate in the 3-12 days following inoculation. Acute interstitial pneumonia and focal adrenal necrosis developed in almost all the animals. About 20% of the mice showed meningoencephalitis and myocarditis. Viral antigen was demonstrated by immunoperoxidase staining in the alveolar walls, around bronchi and blood vessels, and in focal areas of the adrenal cortex as early as 24-48 hours after infection. The virus disseminated probably hematogenously from the lungs and seemed to localize preferentially in the adrenals. In mice surviving the acute stage of infection a subcapsular cell reaction developed in the adrenal cortex. The extensive pneumonia and adrenal necrosis contributed to the high mortality rate of weanling mice infected with HSV-1. The route of viral inoculation and the age of the host animal seemed to influence the localization and outcome of the pathologic process.     

Proliferative processes in the epithelium of colon mucosa in patients with Salmonella infection during first 24 hours after the onset of the disease

DNA synthesis in the epithelium of a distal portion of human colon was studied by radioautography with 3H-thymidine in patients during the first 24 hours of gastrointestinal salmonellosis. All 13 patients aged 18-50 years were admitted to hospital during 9-20 hours after the disease onset. Nobody had a background of gastrointestinal pathology. The control group consisted of samples from sigmoid colon epithelium of 30 healthy individuals. The labelled nuclei index (LNI) was 5.16 +/- 0.27%, the intensity of labelling (IL) was 13.65x +/- 0.82. Endoscopic and pathomorphological studies of colonic mucosa in salmonellosis by the end of the first 24 hours of the disease showed superficial inflammation. Increased LNI (11.48 +/- 1.07%, p < 0.05) characterized activation of proliferation and increased IL (22.24 +/- 2.1, p < 0.05) showed intensification of DNA synthesis. Additionally, in one third of cases enlargement of proliferation compartment up to 2/3 crypt was noticed. It is unlikely that in this situation immune mechanisms play the key role, it seems that a direct stimulation of proliferative processes by a bacterial agent takes place.     

Multiplication and differentiation of glial cells in the optic nerve of the postnatal rat. A reassessment

In order to establish a firm basis for our studies on cell reactivity during Wallerian degeneration in the optic nerve of the rat, gliogenesis in this fiber tract was reassessed. Rats aged 2, 5, 8 and 20 days (key-stages) received a single injection of tritiated thymidine and were sacrificed after a survival period of 1, 3, 5, 10 and 20 days. Before the 5th postnatal day, glioblasts and astrocytes are the only cell types identifiable in the optic nerve. Most of astrocytes undergo their last mitosis during this period. Oligodendrocytes are first seen after the 5th postnatal day, and their maturation proceeds through a regular sequence of light, medium and dark cells. Detailed analysis of this time-course reveals that those precursors of oligodendrocytes that undergo last mitosis at the 5th postnatal day are retarded in their differentiation as compared with those undergoing their last mitosis during the 6-8 days period. When considering glio-axonal interactions, the onset of oligodendrocyte differentiation could proceed in two phases, especially at the 5 day key-stage, with an initial signal triggering the cessation of mitosis of glioblasts and a second signal inducing their maturation, conditioned by the type of surrounding tissue.     

Distribution of exogenous interferon in experimental animals following intratracheal administration]

The distribution of homologous and heterologous interferon in rabbits after intratracheal administration was studied. The content of interferon in the lung tissue decreased 1 hour after injection. At 3 hours the interferon concentration in the lungs in some animals decreased 2-10-fold as compared with the initial. A considerable reduction in interferon content in the lungs was observed 24 hours post-injection. In the blood serum interferon was found in low titers 1, 3 and 6 hours after intratracheal injection. On the contrary, the amount of interferon in the urine increased beginning at 3-6 hours after injection and up to 24-48 hours.     

Regeneration of rat submandibular gland following partial extirpation. A light and electron microscopic study

A wedge of parenchymal tissue was excised from the left submandibular gland of six week old male Sprague-Dawley rats. The animals were randomly grouped by body weight and killed at intervals of one day to five weeks following the operation. Tissue from and adjacent to the site of injury was removed and prepared for routine light and electron microscopy. Light microscopic findings consisted of degeneration and necrosis of the parenchymal tissue during the first 24 hours, followed by hyperemia and endothelial as well as epithelial proliferation from one to three days. Extensive epithelial proliferation occurred during the next two weeks, followed by regeneration of new lobules, beginning at the periphery of the injured lobes. Ultrastructurally, the new parenchymal tissue appeared to have regenerated from residual duct cells. Dedifferentiated epithelial cells gave rise to two different cell lines: one line which transformed into terminal tubules and acinar cells, and another which became striated ducts. These differentiating cells were organizing into lobules as early as three weeks after the operation. Because of their proximity to cells of regenerating striated ducts as well as intercalated ducts and acini, the myoepithelial cells appeared to be of epithelial origin.     

An ultrastructural study of the effect of a diabetogenic dose of alloxan on the secretory ameloblasts of the rat incisor

The effect of a single diabetogenic dose of alloxan on the ameloblasts of enamel secretion was investigated in rat incisor teeth prior to the onset of diabetes mellitus. This was compared with tissue from animals that were sacrificed at the onset of diabetes, and with tissue from animals that had been diabetic for 1 month. Male Sprague-Dawley rats were given a single subcutaneous injection of alloxan at a dose of 150 mg/kg body weight; and the animals were sacrificed at 45 minutes, 2 hours, 24 hours, 48 hours and 29 days after injection. At the electron microscope level the following changes were observed. There was an early accumulation of secretion granules in the vicinity of the Golgi apparatus and within the proximal portion of Tomes' process. These accumulations were present at the onset of diabetes, 24 hours later. At 2 hours after injection a space appeared between the plasma membrane around Tomes' process and the interrod material. This space widened with time, and at 24 hours after injection it became continuous with enlarged intercellular spaces between the proximal portions of Tomes' processes. The widening of the intercellular space was restricted to the area above the distal cell web. At the onset of diabetes this compartment of the cells was similar to that of the control samples. Extracellular material which appeared to be the secretory product of the ameloblast was observed at two sites. On one occasion this material was seen in the wide intercellular spaces between the proximal portions of Tomes' processes 24 hours after injection. It was also seen at the onset of diabetes in the intercellular space at the level of the Golgi apparatus. The changes in the animals that had been diabetic for 1 month were a scarcity of secretion granules within Tomes' processes and an abnormal accumulation of secretion granules within the supranuclear and infranuclear compartents. This study has shown that the toxic effect of alloxan persists up to the time of onset of diabetes mellitus. However, since different morphological changes were observed during diabetes mellitus, it is suggested that the changes caused by diabetes are a separate entity, initially superimposed on and later replacing the acute, toxic effect of the drug.     

缺氧后幼鼠大脑内巢蛋白、神经元特异性烯醇化酶的表达及其对幼鼠学习记忆能力的影响

目的:探讨缺氧对新生大鼠海马区巢蛋白、神经元特异性烯醇化酶(NSE)的表达及幼年大鼠学习记忆能力的影响.方法:将48只7d龄SD大鼠随机分为缺氧组和对照组各24只,缺氧组通过低张性缺氧建立新生鼠缺氧模型.于缺氧24h后,两组各取16只幼鼠取其大脑组织进行巢蛋白、NSE免疫组织化学显色,两组剩余8只大鼠于生后30d Morris水迷宫测试后进行大脑NSE免疫组织化学显色.结果:缺氧组幼鼠海马巢蛋白阳性细胞的积分光密度(IOD)值明显高于对照组,而缺氧组NSE阳性细胞的IOD值明显低于对照组.Morris水迷宫检测中缺氧组幼鼠在目标象限内搜寻时间缩短.结论:缺氧引起新生鼠神经干细胞增殖,却导致神经元数量减少,幼鼠的学习记忆能力明显下降.     

大鼠心脏移植后淋巴细胞5种免疫分子表达的变化

目的：观察大鼠异体异位心脏移植术后不同时间点，淋巴细胞相关免疫分子的表达水平、供心存活率及心肌组织的病理学改变，探讨免疫排斥反应的相关时间进程。方法：分别经供体SD大鼠的心脏主动脉、肺动脉与受体Wistar大鼠的腹主动脉及下腔静脉吻合，进行异位心脏移植术。于术前及术后不同时间点，取血分离淋巴细胞。用流式细胞仪分别检测淋巴细胞上CD4、CD8、IL-2R、ICAM-Ⅰ和MHC-Ⅱ类分子的表达水平。对供心心肌组织进行常规病理学检查。结果：于移植后24h，只有MHC-Ⅱ类分子的表达水平增加，CD4、IL-2R和ICAM—Ⅰ的表达水平降低，CD8无改变。术后72h，CD4、CD8及IL．2R的表达增加，其中CD8和IL-2R达峰值。术后7～10d，除CD4的表达继续增加外，其他4种免疫分子的表达水平逐渐降低。术后不同时间点移植心脏的存活率分别为：100％(24h)、85．7％(72h)、16．7％(7d)、0(10d和12d)。病理学检查显示，移植后24h，心肌组织无明显的病理学变化，术后3d，7只大鼠中4只出现ⅠA级及以上病理改变。术后7d，6只大鼠全部发生Ⅱ级以上的病理学变化。结论：大鼠心脏移植后的24h内，外周血淋巴细胞为以MHC-Ⅱ分子表达为主的抗原识别、呈递期，并伴有一过性免疫功能降低；术后24—72h为T细胞活化期，术后3-7d为免疫排斥反应效应期。CD4、CD8和IL-2R等免疫分子表达的峰值与开始出现轻度排斥反应时病理学变化的时间相一致。     

Autoradiographic study of corneal neovascularization induced by chemical cautery

The corneas of adult rats were cauterized chemically, and the responses of the pericorneal blood vessels and the cellular constituents of the cornea were followed by light microscopic autoradiography after labeling with 3H-thymidine. As in previous experiments, this injury elicited a neovascularization as capillaries sprouted and extended centripetally from the corneoscleral limbus to the cautery site. Chemical cautery induced a response in the epithelium, endothelium, and fibroblasts of the cornea as well as in the vascular cells. Elevated labeling indices for the corneal epithelium and endothelium began at 18 and 21 hours after injury, respectively. In all of these corneal cell types, the labeling index returned to control values by 75 hours. The onset and decline of DNA synthesis in corneal fibroblasts paralleled that of the corneal epithelium and endothelium. Labeling indices of vascular cells (endothelial cells and pericytes) increased 21 hours after injury, reached a maximal level at 45 hours, and returned to control values by 1 month after cautery. The first mitoses in vascular endothelial cells and pericytes were noted 36 hours after injury, and the initial capillary sprouts appeared at 39 hours. This study demonstrates that the thymidine incorporation by cells in the pericorneal blood vessels occurs early within the postcauterization period, at least 15 hours before the first mitotic figures are detected in these same vascular cells. The significance of the temporally related elevations in labeling indices of the vascular cells and the cellular constituents of the corneal cells is uncertain, but there are many potential interrelationships between the controls of cell division and migration for cells of the vessels, epithelium, endothelium, and corneal stroma.     

头部贴敷式亚低温对新生鼠缺氧缺血性脑损伤脑组织中线粒体能量代谢的影响

目的研究头部贴敷式亚低温状态下,新生鼠缺氧缺血性脑损伤时脑组织内能量代谢(ATP、ADP和AMP)的变化,探讨亚低温对缺氧缺血性脑组织的保护机制。方法将88只Wistar新生鼠随机分为4组,分别为假手术常温对照组(CN)、假手术亚低温对照组(CH)、HIBD模型常温恢复组(IN)、HIBD模型亚低温治疗组(IH),每组21只,组内动物再随机分配分为3小组,分别给予常温或亚低温干预,干预持续时间分别为2、6、12h,每个时间点7只动物。结果亚低温治疗组(IH)脑组织中线粒体内ATP、ADP和AMP含量与常温对照组(IN)相比具有差异性(P<0.05)。结论头部贴敷式亚低温可保护脑组织,改善线粒体能量代谢。     

Photoreceptor apoptosis induced by a single systemic administration of N-methyl-N-nitrosourea in the rat retina.

Retinal degeneration was induced by a single intraperitoneal injection of N-methyl-N-nitrosourea in female Sprague-Dawley albino rats at 50 days of age by two dose regimens, which were observed sequentially at 24, 48, and 72 hours and 7, 21, and 35 days after the treatment. After a dose of 75 mg/kg, methylnitrosourea evoked progressive retinal degeneration in all treated rats whereas a dose of 50 mg/kg was less effective. The 75-mg/kg-treated rats showed selective destruction of the photoreceptor cells by an apoptotic mechanism, as confirmed morphologically and by the terminal dUTP nick end labeling method. Apoptosis had already started at 24 hours after the treatment and was completed by day 7. During the photoreceptor degeneration, proliferation of glial fibrillary acidic protein and vimentin-positive Müller cells as detected by proliferating cell nuclear antigen labeling appeared at 48 hours and was prominent 72 hours after the treatment, and macrophage infiltration within the retina as recognized by ED1 positivity was maximal 7 and 21 days after the treatment. Retinal degeneration was also induced in female Brown-Norway colored rats in a similar dose-dependent manner. Pigment epithelium was discontinuous above Bruch's membrane, and migration of the swollen pigment epithelium toward the inner nuclear layer was seen 7 days after the treatment. Therefore, as also confirmed electron microscopically, the most striking change was the destruction of photoreceptor cells by the apoptotic process, followed by Müller cell proliferation, pigment epithelium migration, and macrophage infiltration for cell debris phagocytosis, resulting in a thin remnant of retina with attenuated inner nuclear cells in direct contact with Bruch's membrane or with the pigment epithelium and/or with the Müller cells 35 days after the treatment.