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

Due to its great clinical significance, brain injury following cardiac arrest (CA) has attracted more attention now. Meanwhile, there are currently no approved real time objective methods used to monitor brain injury following CA. In this study, we adopt the method of nonextensive Kullback-Leibler Entropy in investigating the HRV signals from brain injury and compare the result with that of corresponding EEG analysis. The comparative analysis shows that Kullback-Leibler Entropy can reveal the injury level of brain following CA. And we propose a novel quantitative approach for monitoring brain injury.
Algorithms ; Brain ; pathology ; physiopathology ; Brain Ischemia ; physiopathology ; Electroencephalography ; Heart Arrest ; complications ; Heart Rate ; physiology ; Humans

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

OBJECTIVETo elucidate that diffusion weighted imaging (DWI) can be used to predict the injured regions of neonatal brain with hypoxic-ischemic encephalopathy (HIE) in the early phase of injury, and to measure the apparent diffusion coefficient (ADC) values in the multiple regions of the brain.

METHODThe participants in this study were twenty-six infants with HIE from neonatology ward hospitalized between July 2006 and July 2009. Nineteen patients had severe HIE, and seven had moderate HIE. DWI and conventional magnetic resonance imaging (MRI) were performed for each case within the first 72 hrs. The ADC values of eight regions of interest (ROIs) were measured in ten cases with severe HIE (ADC values group). ROIs included posterior limb of internal capsule (PLIC), ventrolateral thalami, basal ganglia, perirolandic cortex, occipital cortex, centrum semiovale, brainstem, and frontal white matter. Twelve neonates were enrolled as the control subjects.

RESULTSDuring the first 72 hrs, the conventional MRI of 26 patients showed subarachnoid hemorrhage in 5, subdural hemorrhage in 2, and mild high signal intensity in the cortex of only one patient. In the 19 cases with severe HIE, abnormal signal intensities were seen in ventrolateral thalami and perirolandic cortex of 17 patients (89%), and the remaining 2 infants showed abnormal cortex and subcortical white matter. In 7 cases with moderate HIE, 4 had abnormal signal intensity in the cortex and subcortical white matter, 2 had abnormal periventricular white matter, and only one showed abnormal signal intensity in the ventrolateral thalami and perirolandic cortex. In the ADC values group, the average ADC values of posterior limb of internal capsule (PLIC), ventrolateral thalami, basal ganglia, perirolandic cortex, occipital cortex, centrum semiovale, brainstem, and frontal white matter respectively were 0.68 (0.56 - 0.88), 0.73 ± 0.13, 0.67 ± 0.11, 0.78 ± 0.22, 0.90 ± 0.16, 0.87 ± 0.21, 0.73 ± 0.19, 1.32 ± 0.22 × 10(-3) mm(2)/S. In the control group, the average ADC values of posterior limb of internal capsule (PLIC), ventrolateral thalami, basal ganglia, perirolandic cortex, occipital cortex, centrum semiovale, brainstem, and frontal white matter respectively were 0.96 (0.95 - 1.02), 1.02 ± 0.90, 1.15 ± 0.99, 1.08 ± 0.07, 1.09 ± 0.08, 1.39 ± 0.20, 0.96 ± 0.05, 1.58 ± 0.18× 10(-3) mm(2)/S. There was statistically significant difference in the average ADC values between each of 8 ROIs of infants with HIE and healthy neonates (P < 0.01).

CONCLUSIONIn the first days after birth, the major injured regions of severe HIE were ventrolateral thalami and perirolandic cortex, the minor injured regions were cortex and subcortical white matter. Multiple regions of moderate HIE were injured, including cortex with subcortical white matter, periventricular white matter, and ventrolateral thalami with perirolandic cortex. The ADC values of the regions with abnormal signal intensity decreased, also some regions with the normal signal intensity.

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

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