We have tracked the response of host and transplanted neural progenitors or stem cells to hypoxic-ischemic (HI) brain injury, and explored the therapeutic potential of neural stem cells (NSCs) injected into mice brains subjected to focal HI injury. Such cells may integrace appropriately into the degenerating central nervous system (CNS), and showed robust engraftment and foreign gene expression within the region of HI inury. They appeared to have migrated preferentially to the site of ischemia, experienced limited proliferation, and differentiated into neural cells lost to injury, trying to repopulate the damaged brain area. The transplantation of exogenous NSCs may, in fact, augment a natural self-repair process in which the damaged CNS "attempts" to mobilize its own pool of stem cells. Providing additional NSCs and trophic factors may optimize this response. Therefore, NSCs may provide a novel approach to reconstituting brains damaged by HI brain injury. Preliminary data in animal models of stroke lends support to these hypotheses.
Animal ; Brain/pathology ; Brain Diseases/therapy* ; Brain Diseases/pathology ; Brain Ischemia/therapy* ; Brain Ischemia/pathology ; Gene Therapy* ; Human ; Nerve Tissue/cytology* ; Stem Cells/transplantation* ; Tissue Therapy*

Humans ; Hypoxia-Ischemia, Brain ; pathology ; Infant, Newborn ; Magnetic Resonance Imaging

Acupuncture Therapy ; Apoptosis ; Brain Ischemia ; pathology ; therapy ; Humans

AIMTo observe the effect of nonselective nitro oxide synthase inhibitor N(G)-nitro-L-arginine(L-NA) on mitochondria injury in focal cerebral ischemia rats.

METHODSThe rats were randomly divided into sham, ischemia and L-NA treatment group. The model of focal cerebral ischemia was prepared with thread embolism in rats. L-NA was administrated respectively at 2 h, 6 h, 12 h after middle cerebral artery occlusion (MCAO). Rats were killed and the mitochondria of cerebral tissue were isolated by differential centrifugation after L-NA treatment for 3 days. The swelling and the activity of mitochondria, and the activities of ATPase, SOD, GSH-Px in mitochondria and the contents of NO, MDA in mitochondria were measured. Ultrastructure changes of neuronal mitochondria were examined by electronic microscope in ischemia and L-NA treatment group.

RESULTSThe swelling of mitochondria was markedly increased and the activity of mitochondria was decreased, and the contents of mitochondria NO and MDA were markedly increased, the activity of ATPase, SOD and GSH-Px in mitochondria were decreased significantly after MCAO. Compared with ischemia group, the contents of NO were decreased after ischemia 2h, 6h, 12h administered by L-NA, and the swelling of mitochondria was decreased and the activity of mitochondria was increased, and the activities of ATPase, SOD, GSH-Px in mitochondria were enhanced and the contents of MDA in mitochondria were decreased after ischemia 12 h administered by L-NA. The neuronal cytoplasm and the mitochondria swelled, the cristae were disrupted, dissolved or disappeared in MCAO rats. Administration of L-NA could reduce these changes induced by cerebral ischemia in rats.

CONCLUSIONIt could be concluded that L-NA could beneficially inhibit NO production. But it could't protect brain against damage in ischemia acute stage. It could improve mitochondria energy pump, ameliorate oxidative injury and increase the activities of mitochondria during postischemia, and then could effectively protect brain against damage induced by focal cerebral ischemia.

Animals ; Arginine ; pharmacology ; Brain ; metabolism ; Brain Ischemia ; metabolism ; pathology ; Male ; Mitochondria ; metabolism ; pathology ; Rats ; Rats, Wistar

It is known that ischemic cerebrovascular disease is causing enormous harm to human health on account of the resultant high morbidity and disability rate. In this connexion, the anticipated target is to control the size of focal ischemic cerebral infarction, which is also an important method for judgment of therapeutic efficacy. The key question is to survey the size accurately and objectively; at the same time, the quantitative analysis of focal ischemic cerebral infarction is the pivotal question affecting the experiment conclusion and the reliability level. In this paper are introduced and summarized the methods being recently and commonly used in survey and computation, and the studies made on quantitative analysis of focal ischemic cerebral infarction by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining method. Also are summarized the principles of dyeing in TTC method, the preparatory work, and the commonly used method of surveying and computation. It is the intent of this review to provide relevant data and suggestion for research workers.
Animals ; Brain Ischemia ; pathology ; Cerebral Infarction ; pathology ; Coloring Agents ; Humans ; Reperfusion Injury ; pathology ; Tetrazolium Salts

Immunohistochemistry and double immunofluorescent labeling techniques combined with confocal laser scanning microscope analysis were used to investigate the characteristic spatial induction profile of nestin following a transient middle cerebral artery occlusion in adult rat brain. The results showed that nestin was induced in ischemic core at 1 day after reperfusion. In addition to ischemic core, the expression of nestin increased in peri-ischemic I, II and III regions at 3 days and 1 week, then it decreased and narrowed along the rim of ischemic core 2 weeks after reperfusion. Double immunofluorescent labeling showed that nestin positive cells were mostly co-stained with GFAP,a astrocyte marker, in peri-ischemic I region 3 days after reperfusion. At 2 weeks, however nestin cells showed a long process and the cells double stained with nestin and NSE,a neuonal specific marker,increased in the ischemic brain. The results suggest that cerebral ischemia induces nestin expression in damaged neurons which might favor the neuroprotection against ischemic damage.
Animals ; Brain ; metabolism ; pathology ; Brain Ischemia ; metabolism ; pathology ; Immunohistochemistry ; Infarction, Middle Cerebral Artery ; metabolism ; pathology ; Nestin ; metabolism ; Neurons ; metabolism ; Rats

Retrograde cerebral perfusion under hypothermic circulatory arrest is a simple and useful adjunct to avoid cerebral ischemic injury in the treatment of aortic arch pathology. In the surgery of distal aortic arch and proximal descending aortic lesions through the left thoracotomy incision, right atrium-retrograde cerebral perfusion (RA-RCP) through a venous cannula positioned into the right atrium is simpler than retrograde cerebral perfusion through superior vena cava. The time limits for RA-RCP during aortic arch reconstruction have yet to be clarified. We, herein, present a case with uneventful recovery after RA-RCP of 94 minutes during reconstruction of aortic arch and descending aorta. These data suggest that RA-RCP, as an adjunct to hypothermic circulatory arrest, may prolong the circulatory arrest time and thus prevent ischemic injury of the brain, even when RA-RCP exceeds 90 minutes.
Aneurysm, Dissecting ; Aorta, Thoracic* ; Brain ; Brain Ischemia ; Catheters ; Heart Atria ; Pathology ; Perfusion* ; Thoracotomy ; Vena Cava, Superior

The authors compared the changes of morphology, blood brain barrier alteration, pathology, arterial blood lactate content and cerebrospinal fluid lactate content between an intermittent brain retraction group and a continuous brain retraction group in 56 mongrel cats. The results were as follows ; 1) Microscopically, hemorrhages were punctate in 15 cases among 25 cases in the intermittent retraction group. However, there were multiple or large hemorrhages in 13 cases among the 25 cases in the continuous brain retraction group. 2) All cases of the intermittent retraction group showed 0~25% Evans blue staining of the coronal section crossing the retraction site. However, 8 cases among the 25 cases of the continuous retraction group showed 51~75% Evans blue staining and 4 cases of this group showed 76~100% staining. 3) With photomicroscopy, the authors noted small hemorrhage and cellular swelling in the intermittent retraction group instead of pyknosis, hemorrhagic necrosis, vacuolation in the continuous retraction group. 4) The change of arterial blood lactate content was from 1.22+/-0.24mmol/L at preretraction time to 1.42+/-0.26mmol/L at 90 minutes after release of retractor in the intermittent retraction group(p<0.01). In the continuous retraction group, the authors noted a change in the lactate content from 1.20+/-0.38mmol/L to 3.15+/-0.97mmol/L for the same time as above(p<0.001). 5) The change of CSF lactate content in the intermittent retraction group was from 1.39+/-0.29mmol/L at preretraction time to 1.43+/-0.23mmol/L at 90 minutes after release of retractor(p>0.05). In the continuous retraction group, this author noted change in the lactate content from 1.37+/-0.28mmol/L to 2.11+/-0.52mmol/L for the same time as described above(p<0.01). From the above results, the superiority of the intermittent brain retraction was demonstrated as compared with the continuous brain retraction. Also the possible utilization of this experimental method was discussed for other wxperimental studies on ischemia.
Animals ; Blood-Brain Barrier ; Brain* ; Cats* ; Cerebrospinal Fluid ; Evans Blue ; Hemorrhage ; Ischemia ; Lactic Acid ; Necrosis ; Pathology

BACKGROUNDMild hypoxic-ischemic encephalopathy (HIE) injury is becoming the major type in neonatal brain diseases. The aim of this study was to assess brain maturation in mild HIE neonatal brains using total maturation score (TMS) based on conventional magnetic resonance imaging (MRI).

METHODSTotally, 45 neonates with clinically mild HIE and 45 matched control neonates were enrolled. Gestated age, birth weight, age after birth and postmenstrual age at magnetic resonance (MR) scan were homogenous in the two groups. According to MR findings, mild HIE neonates were divided into three subgroups: Pattern I, neonates with normal MR appearance; Pattern II, preterm neonates with abnormal MR appearance; Pattern III, full-term neonates with abnormal MR appearance. TMS and its parameters, progressive myelination (M), cortical infolding (C), involution of germinal matrix tissue (G), and glial cell migration bands (B), were employed to assess brain maturation and compare difference between HIE and control groups.

RESULTSThe mean of TMS was significantly lower in mild HIE group than it in the control group (mean ± standard deviation [SD] 11.62 ± 1.53 vs. 12.36 ± 1.26, P < 0.001). In four parameters of TMS scores, the M and C scores were significantly lower in mild HIE group. Of the three patterns of mild HIE, Pattern I (10 cases) showed no significant difference of TMS compared with control neonates, while Pattern II (22 cases), III (13 cases) all had significantly decreased TMS than control neonates (mean ± SD 10.56 ± 0.93 vs. 11.48 ± 0.55, P < 0.05; 12.59 ± 1.28 vs. 13.25 ± 1.29, P < 0.05). It was M, C, and GM scores that significantly decreased in Pattern II, while for Pattern III, only C score significantly decreased.

CONCLUSIONSThe TMS system, based on conventional MRI, is an effective method to detect delayed brain maturation in clinically mild HIE. The conventional MRI can reveal the different retardations in subtle structures and development processes among the different patterns of mild HIE.

Brain ; pathology ; Female ; Humans ; Hypoxia-Ischemia, Brain ; diagnosis ; Infant, Newborn ; Magnetic Resonance Imaging ; methods ; Male

OBJECTIVETo establish a new macrophotographic measurement of brain surface area to evaluate brain edema after focal cerebral ischemia in mice.

METHODSPermanent focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in mice. The brains were removed 10,30 min,1,3,6,12 and 24 h after MCAO, and photographed in dorsal and lateral views by a digital camera. Then, 6 coronal slices of 1 mm thick were cut and photographed. Finally, the water content of brain tissue was measured by heating at 110 degrees C for 24 h. The left and right hemisphere areas of the brains and the brain slices were analyzed and calculated by MedBrain 2 imaging analyzer to evaluate brain edema.

RESULTThe macrophotographic measurement showed that the ischemic hemisphere areas significantly increased from 1 h after focal cerebral ischmia, which was similar to the measurement of water content. This measurement for brain edema correlated well with those of water content and brain slice volume.

CONCLUSIONThe macrophotographic measurement is an objective and quantitative method for evaluating brain edema after focal cerebral ischemia.

Animals ; Brain Edema ; diagnosis ; pathology ; Brain Ischemia ; complications ; psychology ; Female ; Mice ; Mice, Inbred ICR ; Photography