Biomedical subjects

Anil Nanda

Publications and source records attributed to Anil Nanda.

At least 55 records · Page 3Linked to original sources

PubMed2004

Mechanisms of erythropoietin-induced brain protection in neonatal hypoxia-ischemia rat model.

Erythropoietin, a hemotopoietic growth factor, has brain protective actions. This study investigated the mechanisms of Recombinant Human EPO (rhEPO)-induced brain protection in neonates. An established rat hypoxia-ischemia model was used by ligation of the right common carotid artery of 7-day-old pups, followed by 90 minute of hypoxia (8% 02 and 92% N2) at 37 degrees C. Animals were divided into three groups: control, hypoxia-ischemia, and hypoxia-ischemia plus rhEPO treatment. In rhEPO treated pups, 300 units rhEPO was administered intraperitoneally 24 hours before hypoxia. rhEPO treatment (300 units) was administered daily for an additional 2 days. ELISA and immunohistochemistry examined the expression of EPO and EPOR. Brain weight, morphology, TUNEL assay, and DNA laddering evaluated brain protection. rhEPO abolished mortality (from 19% to 0%) during hypoxia insult, increased brain weight from 52% to 88%, reduced DNA fragmentation, and decreased TUNEL-positive cells. Real-time RT-PCR, Western blot, and immunohistochemistry revealed an enhanced expression of heat shock protein 27 (HSP27) in ischemic brain hemisphere. Double labeling of TUNEL with HSP27 showed most HSP27 positive cells were negative to TUNEL staining. rhEPO reduces brain injury, especially apoptotic cell death after neonatal hypoxia-ischemia, partially mediated by the activation of HSP27.

Animals↗

PubMed2004

Signaling pathways for early brain injury after subarachnoid hemorrhage.

Few studies have examined the signaling pathways that contribute to early brain injury after subarachnoid hemorrhage (SAH). Using a rat SAH model, the authors explored the role of vascular endothelial growth factor (VEGF) and mitogen-activation protein kinase (MAPK) in early brain injury. Male Sprague-Dawley rats (n = 172) weighing 300 to 350 g were used for the experimental SAH model, which was induced by puncturing the bifurcation of the left anterior cerebral and middle cerebral arteries. The blood-brain barrier (BBB), brain edema, intracranial pressure, and mortality were evaluated at 24 hours after SAH. The phosphorylation of VEGF and different MAPK subgroups (ERK1/2, p38, and JNK) were examined in both the cortex and the major cerebral arteries. Experimental SAH increased intracranial pressure, BBB permeability, and brain edema and produced high mortality. SAH induced phosphorylation of VEGF and MAPKs in the cerebral arteries and, to a lesser degree, in the cortex. PP1, an Src-family kinase inhibitor, reduced BBB permeability, brain edema, and mortality and decreased the phosphorylation of VEGF and MAPKs. The authors conclude that VEGF contributes to early brain injury after SAH by enhancing the activation of the MAPK pathways, and that the inhibition of these pathways might offer new treatment strategies for SAH.

Animals↗

PubMed2004

Platelet-leukocyte-endothelial cell interactions after middle cerebral artery occlusion and reperfusion.

The adhesion of both leukocytes and platelets to microvascular endothelial cells has been implicated in the pathogenesis of ischemia/reperfusion (I/R) injury in several vascular beds. The objectives of this study were to (1) assess the platelet-leukocyte-endothelial cell interactions induced in the cerebral microvasculature by middle cerebral artery occlusion (MCAO)/reperfusion, and (2) define the molecular determinants of the prothrombogenic and inflammatory responses in this model of focal I/R. MCAO was induced for 1 hour in wild-type (WT) mice, WT mice treated with a monoclonal antibody (mAb) to either P-selectin or GPIIb/IIIa, and in P-selectin-/-(P-sel-/-) chimeras. Isolated platelets labeled with carboxyfluorescein diacetate succinimidyl ester (CFDASE) were administered intravenously and observed with intravital fluorescence microscopy. Leukocytes were observed after intravenous injection of rhodamine 6G. One hour of MCAO followed by 1 hour of reperfusion resulted in the rolling and adhesion of leukocytes in venules, and after 4 hours of reperfusion, the adhesion of both leukocytes and platelets was detected. Although both the P-selectin and GPIIb/IIIa mAbs significantly reduced the adhesion of leukocytes and platelets at 4 hours of reperfusion, the antiadhesive effects of the P-selectin mAb were much greater. The leukocyte and platelet adhesion responses were significantly attenuated in both P-sel-/- --> WT and WT --> P-sel-/- bone marrow chimeras, compared with WT --> WT chimeras. Neutropenia, induced by antineutrophil serum treatment, also reduced the recruitment of leukocytes and platelets after cerebral I/R. These findings implicate a major role for both platelet-associated and endothelial cell-associated P-selectin, as well as neutrophils in the inflammatory and prothrombogenic responses in the microcirculation after focal cerebral I/R.

Animals↗

PubMed2004

Mmp-9 deficiency enhances collagenase-induced intracerebral hemorrhage and brain injury in mutant mice.

Matrix metalloproteinase-9 (MMP-9) participates in the disregulation of blood-brain barrier during hemorrhagic transformation, and exacerbates brain injury after cerebral ischemia. However, the consequences of long-term inhibition or deficiency of MMP-9 activity (which might affect normal collagen or matrix homeostasis) remains to be determined. The authors investigated how MMP-9 gene deficiency enhances hemorrhage and increases mortality and neurologic deficits in a collagenase-induced intracerebral hemorrhage (ICH) model in MMP-9-knockout mice. MMP-9-knockout and corresponding wild-type mice at 20 to 35 weeks were used to model an aged population (because advanced age is a significant risk factor in human ICH). Collagenase VII-S (0.5 microL, 0.075 U) was injected into the right basal ganglia in mice and mortality, neurologic deficits, brain edema, and hemorrhage size measured. In addition, MMP-9 activity, brain collagen content, blood coagulation, cerebral arterial structure, and expressions of several MMPs were examined. Increased hemorrhage and brain edema that correlated with higher mortality and neurologic deficits were found in MMP-9-knockout mice. No apparent structural changes were observed in cerebral arteries, even though brain collagen content was reduced in MMP-9-knockout mice. MMP-9-knockout mice did exhibit an enhanced expression of MMP-2 and MMP-3 in response to ICH. The results indicate that a deficiency of MMP-9 gene in mutant mice increases collagenase-induced hemorrhage and the resulting brain injury. The intriguing relationship between MMP-9 deficiency and collagenase-induced ICH may reflect the reduction in collagen content and an enhanced expression of MMP-2 and MMP-3.

Animals↗

PubMed2004

Role of AT1 receptors and NAD(P)H oxidase in diabetes-aggravated ischemic brain injury.

The objective of the present study was to examine the role of the angiotensin II type 1 receptor (AT(1)-R) in the diabetes-aggravated oxidative stress and brain injury observed in a rat model of combined diabetes and focal cerebral ischemia. Diabetes was induced by an injection of streptozotoxin (STZ; 55 mg/kg iv) at 8 wk of age. Two weeks after the induction of diabetes, some animals received continuous subcutaneous infusion of the AT(1)-R antagonist candesartan (0.5 mg.kg(-1).day(-1)) for 14 days. Focal cerebral ischemia, induced by middle cerebral artery occlusion/reperfusion (MCAO), was conducted at 4 wk after STZ injection. Male Sprague-Dawley rats (n = 189) were divided into five groups: normal control, diabetes, MCAO, diabetes + MCAO, and diabetes + MCAO + candesartan. The major observations were that 1) MCAO produced typical cerebral infarction and neurological deficits at 24 h that were accompanied by elevation of NAD(P)H oxidase gp91(phox) and p22(phox) mRNAs, and lipid hydroperoxide production in the ipsilateral hemisphere; 2) diabetes enhanced NAD(P)H oxidase gp91(phox) and p22(phox) mRNA expression, potentiated lipid peroxidation, aggravated neurological deficits, and enlarged cerebral infarction; and 3) candesartan reduced the expression of gp91(phox) and p22(phox), decreased lipid peroxidation, lessened cerebral infarction, and improved the neurological outcome. We conclude that diabetes exaggerates the oxidative stress, NAD(P)H oxidase induction, and brain injury induced by focal cerebral ischemia. The diabetes-aggravated brain injury involves AT(1)-Rs. We have shown for the first time that candesartan reduces brain injury in a combined model of diabetes and cerebral ischemia.

Animals↗

PubMed2004

Transradial approach to coil embolization of an intracranial aneurysm.

PURPOSE: To report the use of a transradial approach to coil embolization of an intracranial aneurysm in a morbidly obese patient. TECHNICAL NOTE: When the transfemoral approach was inaccessible in a morbidly obese patient with a ruptured intracranial aneurysm, coil embolization was performed via a 6-F sheath placed in the radial artery. Multiple platinum coils were delivered to exclude the 14-mm basilar tip aneurysm. Because heparin was not reversed, the sheath was left in the artery for 24 hours then removed. The radial artery was pulsatile, and blood supply to the hand was good. CONCLUSIONS: The radial artery appears to be a suitable route for access to the intracranial vessels when the femoral artery is not available.

Adult↗

PubMed2004

Gamma knife surgery in the management of brain metastases from lung carcinoma: a retrospective analysis of survival, local tumor control, and freedom from new brain metastasis.

OBJECT: The objective of this retrospective study was to analyze the results of stereotactic radiosurgery performed using a gamma knife in the treatment of 44 consecutive patients with brain metastases from lung carcinoma. METHODS: Forty-four patients with lung carcinoma were treated for metastatic brain tumors by performing radiosurgery with a Leksell Gamma Knife. Twenty-one patients (47.7%) were women and 23 were men. The mean age of the patients was 56 years (range 35-77 years). Twenty-two patients (50%) had solitary tumors and the rest had multiple tumors (two-six lesions). Eighteen patients (40.9%) presented with a recurrent and/or progressive brain disease that previously had been treated with other modalities (surgery, external-beam radiotherapy, or both). Fifteen patients had controlled lung disease and 19 patients had systemic metastases (in lymph nodes, liver, and/or bones) at the time of radiosurgery. The median follow-up period was 18.25 months. All patients were followed up for three different end points: 1) death caused by the disease; 2) clinical and/or radiological evidence of progression of the tumor that had been treated with radiosurgery; and 3) appearance of new lesions. At the last follow-up review, 17 patients (38.6%) were alive and 27 (61.4%) had died. Ten patients (22.7%) died as a result of brain disease (failure of local control or new metastases). Controlled primary disease at the time of detection of metastases and the ability to achieve local tumor control after radiosurgery significantly improved the patient survival (p < 0.01). Control of the treated tumor(s) was achieved in 32 of 44 patients (72 tumors) and 10 patients experienced treatment failure. In addition to the 44 patients comprising the study population, two other patients were treated, but died of lung disease too early in the follow-up period to have been assessed. As of the last follow-up review, no new brain metastasis had occurred in 36 patients (81.8% [includes surviving and nonsurviving patients]). The median duration of overall survival was 7 months, the median period of controlled brain disease was 21 months, and the median period of freedom from new brain metastases was 17 months (95% confidence interval 13-19 months). CONCLUSIONS: Gamma knife surgery has significantly reduced the incidence of mortality from brain disease by effectively accomplishing local tumor control in patients with metastatic lung cancer. Local control and freedom from new brain metastases is not influenced by prior external-beam radiotherapy.

Adult↗

PubMed2004

Metastatic lesions involving the sella: report of three cases and review of the literature.

Metastatic cancer must be considered as a possibility for intrasellar masses. Newer treatment modalities, such as gamma knife radiosurgery needs to be explored for these lesions. Three cases of intrasellar metastatic lesions were retrospectively reviewed. Presenting complaints, radiographic studies, operative procedure, and histopathological confirmation were recorded for each patient. All had an unknown primary malignancy prior to the presentation with the intrasellar lesion detected by magnetic resonance imaging (MRI). Presenting symptoms were diplopia with extraocular movement deficits in all patients. Transsphenoidal resection or biopsy was performed. Histopathological analysis revealed small cell carcinoma in two patients and plasmacytoma in one. All patients received postoperative radiation and/or chemotherapy. Survival following initial presentation was 2 months and 6 months for two of the patients; the third patient is alive at 2-month follow-up.

Aged↗

PubMed2003

Cerebral microvascular responses to hypercholesterolemia: roles of NADPH oxidase and P-selectin.

Although hypercholesterolemia is widely accepted as a major risk factor for coronary artery and peripheral vascular diseases, its role in the pathogenesis of stroke is controversial. The objectives of this study were to determine how hypercholesterolemia affects the cerebral microcirculation under resting conditions and after ischemia-reperfusion (I/R). Platelet- and leukocyte-endothelial cell interactions and oxidant production (using the oxidant-sensitive fluorochrome dihydrorhodamine-123) were monitored by intravital videomicroscopy in the cerebral microvasculature of mice placed on either a normal (ND) or cholesterol-enriched diet (HCD). Platelets labeled with carboxyfluorescein diacetate succinimidyl ester (CFDASE) and leukocytes labeled with rhodamine 6G were seen to roll and firmly adhere, with a corresponding increase in oxidant production, in venules of mice on HCD, but not ND. Immunoneutralization of P-selectin attenuated the platelet- and leukocyte-endothelial cell interactions and the enhanced oxidant production associated with HCD. A GPIIb/IIIa blocking antibody did not alter the blood cell-vessel wall interactions to HCD. Mice deficient in the NADPH oxidase subunit gp91(phox) exhibited significantly blunted platelet and leukocyte recruitment responses to HCD. Focal I/R also elicited inflammatory and prothrombogenic responses in cerebral venules and these were exaggerated in mice on HCD. These results implicate an oxidant-dependent, P-selectin-mediated mechanism in the blood cell-vessel wall interactions induced by hypercholesterolemia in the brain and demonstrate that the deleterious effects of I/R on the brain are exacerbated by this cardiovascular risk factor.

Animals↗

PubMed2003

HBO suppresses Nogo-A, Ng-R, or RhoA expression in the cerebral cortex after global ischemia.

Nogo-A, a myelin-associated neurite outgrowth inhibitory protein, binds with the Ng-R receptor to activate RhoA intracellular signals and inhibit the plasticity after CNS injury. We evaluated the effect of hyperbaric oxygen (HBO) on the expression of Nogo-A, Ng-R, and RhoA after transient global ischemia in a rat 2 vessel occlusion global ischemic model. Male SD rats (n=78) were randomly divided into 13 groups: 1 sham group, 6 groups of global ischemia, and 6 groups of HBO treatment after global ischemia. HBO (3ATA) was applied for 2 hr at 1 hr after global ischemia. Rats were sacrificed at 6, 12, 24, 48, and 96 hr and 7 days. Global ischemia (10 min) produced a marked increase of Nogo-A/B, Nogo-A, Ng-R, and RhoA expression. Immunohistochemistry showed increased Nogo-A/B and Nogo-A located in the myelin sheath of ischemic brain cortex. Ng-R expressed on the surface of neurons and their processes, and RhoA expressed inside the cytoplasm of neurons in ischemic brain. HBO significantly reduced neurological injury, decreased the levels of Nogo-A, Ng-R, and RhoA in ischemic injured cortex (p<0.05).

Animals↗

PubMed2003

Molecular determinants of the prothrombogenic and inflammatory phenotype assumed by the postischemic cerebral microcirculation.

BACKGROUND AND PURPOSE: Circulating blood cells have been implicated in the pathogenesis of cerebral ischemia/reperfusion (I/R) injury and stroke. The objective of this study was to define the magnitude and molecular determinants of the platelet- and leukocyte-endothelial cell adhesive interactions induced by I/R in the mouse brain. METHODS: Bilateral common carotid artery occlusion was induced for 1 hour in C57BL/6 mice, followed by either 40 minutes or 4 hours of reperfusion. Fluorescent platelets were administered intravenously, and the frontal brain surface was observed with intravital fluorescence microscopy. Leukocyte-endothelial cell adhesion was monitored with the use of rhodamine-6G. RESULTS: Ischemia followed by 40 minutes of reperfusion resulted in the rolling (125.1+/-23.6/mm2) and firm adhesion (109.5+/-25.8/mm2) of leukocytes but not platelets in venules. However, with 4 hours of reperfusion, rolling (138.8+/-24.6/mm2) and firm adhesion (153.7+/-22.3/mm2) of platelets were detected, and this was accompanied by a more intense recruitment of rolling (374.5+/-54.6/mm2) and adherent (445.2+/-57.1/mm2) leukocytes. In mice deficient in either P-selectin (P-selectin-/-) or intercellular adhesion molecule-1 (ICAM-1) (ICAM-1-/-), the I/R-induced platelet-endothelial cell (by 80% and 60%, respectively) and leukocyte-endothelial cell (by 84% and 78%, respectively) interactions were significantly blunted compared with those of wild-type mice. CONCLUSIONS: These findings indicate that I/R promotes the adhesion of both platelets and leukocytes in cerebral venules, with the accumulation of adherent leukocytes preceding the recruitment of platelets. Both P-selectin and ICAM-1 contribute to the inflammatory and prothrombogenic state induced by cerebral I/R.

Animals↗

PubMed2003

Management of carotid artery injuries: Louisiana State University Shreveport experience.

BACKGROUND: Traumatic carotid artery injury is an infrequently encountered surgical entity. Carotid artery injuries in polytrauma patients can be easily missed in the absence of clinical findings and/or presence of confounding concurrent injuries. METHODS: Between 1991 and 1998, 23 patients were diagnosed with various carotid artery injuries at the trauma center of Louisiana State University Health Sciences Center, Shreveport, Louisiana. Injuries were assessed by angiography and/or surgical exploration of the neck. Clinical presentations, radiologic features, management strategies, and neurologic outcomes were statistically analyzed and compared with the existing literature. RESULTS: Twelve patients (52%) had penetrating carotid artery injuries, while 11 (48%) had blunt trauma. The diagnosis of carotid injury was significantly delayed in the group with blunt trauma as opposed to those with penetrating wounds. Surgical repair was performed in 6 (26%) patients; 2 (8%) underwent balloon occlusion, while ligation was conducted in 2 (8%) patients. Thirteen patients (57%) were treated conservatively with anticoagulants. Six patients (26%) died, while another 6 (26%) had permanent neurologic deficit. Mortality and morbidity was significantly higher in the group with penetrating injuries. A statistical analysis showed that multi-level carotid injury (p < 0.002) and increasing age (p < 0.001) had a significantly higher mortality. CONCLUSIONS: Injury to carotid arteries results in significant mortality and morbidity. Our results indicate that penetrating carotid injury at more than one level carries higher mortality and morbidity rates than blunt injury. Furthermore, early identification of the injured segment may favorably influence the outcome for such patients.

Academic Medical Centers↗

PubMed2003

Multicentric glioblastoma multiforme determined by positron emission tomography: a case report.

UNLABELLED: The actual incidence of true multicentric glioblastoma multiforme (GBM) varies between 2.4 and 4.9% of all GBMs. True multicentric tumors are described as widespread lesions in different lobes or hemispheres, which cannot be explained by spreading along the cerebrospinal fluid or blood pathways. We present here a case of multicentric GBM identified with positron emission tomography. CASE REPORT: A 73-year-old woman with sudden onset headaches, balance problems, and one episode of syncope was diagnosed as having an irregular, contrast-enhancing, space-occupying lesion in the left-temporal-parietal region on magnetic resonance imaging (MRI). The tissue diagnosis was confirmed as GBM, and she received stereotactic radiosurgery using the Leksell Gamma Knife (Elekta Instruments, Atlanta, GA). A 3-month, follow-up, MRI scan showed a remarkable decrease in the size of the contrast-enhancing area that was targeted during radiosurgery. A suspicious area of enhancement was detected on the right side, although no surrounding edema was evident. Fluorodeoxyglucose (FDG)-PET scanning revealed a large irregular neoplasm extending from the inferior left-temporal lobe into the deep parietal lobe with extremely intense FDG uptake, suggesting a very aggressive tumor. A smaller lesion was also discovered in the deep right-frontal lobe, representing a second neoplastic focus. The patient refused any further treatment. CONCLUSION: PET scans, in conjunction with MRI scans, allow for the best possible and most comprehensive diagnosis and treatment plans.

Aged↗

PubMed2003

Signal transduction pathways in cerebral vasospasm.

Cerebral vasospasm is a deadly complication following the rupture of intracranial aneurysms. The time course of cerebral vasospasm is unique in that it is slow developing, usually takes 4-7 days to peak, but lasts up to 2-3 weeks, and is resistant to most known vasodilators. These special features make cerebral vasospasm the most important determinant in the outcome of patients suffering subarachnoid hemorrhage. The available treatment strategies include mechanical dilation of spastic cerebral arteries (angioplasty) and non-selective vasodilatation such as by Ca(2+) channel blockers. One new development in the experimental treatment of cerebral vasospasm is the looming target of signaling pathways. Understanding vasospastic signals in cerebral arteries might offer a new avenue for selective treatment of cerebral vasospasm in the future.

Journal Article↗

PubMed2003

Solitary tuberculoma of the cerebellopontine angle: a rare presentation.

Central nervous system tuberculoma presenting as a solitary mass in an extrinsic location is rare. Due to the increase in incidence of tuberculosis in the western world, there is a corresponding increase in CNS tuberculosis. Cerebellopontine angle tumours are most commonly acoustic schwannomas or meningiomas. Radiosurgery as a primary modality of treatment for many CNS masses without prior pathological diagnosis is increasing in popularity. This report shows that a mass in the CP angle can closely mimic a tumour radiologically and inappropriate radiation treatment was avoided after surgery. Histopathological examination proved it to be a tuberculoma. Awareness of this rare presentation of a solitary tuberculoma in the CP angle is emphasised.

Brain Neoplasms↗

PubMed2003

Microsurgery for Potential Radiosurgical Skull Base Lesions: A Retrospective Analysis and Comparison of Results.

The outcomes of 26 complex skull base tumors treated with microsurgery were compared with the outcomes of similar tumors treated with radiosurgery as reported in the literature. The University neurosurgery database was searched for patients who underwent microsurgery for the treatment of skull base tumors between 1990 and 2001 at Louisiana State University Health Sciences Center in Shreveport, Louisiana. Twenty-six skull base meningiomas treated by microsurgery by the senior author (AN) were identified retrospectively. On imaging, the tumors were well defined and less than 3 cm in the greatest diameter, making them ideal candidates for a radiosurgical procedure had this modality been available. The follow-up and outcomes of these 26 patients were compared with the published outcomes of similar tumors treated with radiosurgery. Total excision was achieved in 17 (65.3 %) patients. Excision was subtotal in 9 (34.6 %) patients due to the critical locations of their tumors. The median hospital stay for these patients was 4 days (range, 3 to 12 days). Two patients (7.6 %) had transient cerebrospinal fluid leaks from the wound, and 2 (7.6 %) had transient facial paresis. Overall, preoperative symptoms improved in 23 (88.4 %) patients. The median follow-up was 56 months (range, 3 to 120 months). The overall survival rate for all was 87.2 +/- 3.7 % at 50 months. Two patients (7.6 %) subsequently underwent repeat surgery for a recurrent or progressive disease. The actuarial 8-year tumor control rate was 86.4 +/- 4.4 % using the Kaplan-Meier method. For small skull base tumors with benign histology, microsurgery is as safe and effective a treatment option as stereotactic radiosurgery. The symptomatic improvement in patients is better with microsurgery than with radiosurgery because the volume of the tumor is reduced immediately. A combined approach using both modalities is usually needed for larger tumors when attempts at total resection would jeopardize the neurologic function of the patient.

Journal Article↗

PubMed2003

Management of intracranial aneurysms: factors that influence clinical grade and surgical outcome.

BACKGROUND: We report the experience in managing intracranial aneurysms at our medical center. METHODS: We retrospectively analyzed 297 intracranial aneurysms managed during a 6-year period. Risk factors were analyzed with respect to their influence on outcome after surgery as measured by Glasgow Outcome Scale score. RESULTS: Fifty-eight patients had multiple aneurysms. Of all aneurysms, 83% were in the anterior circulation, 37% were unruptured, and 59% were larger than 10 mm in size. Good outcomewas achieved in 75% of patients, and another 16% had fair outcomes. The mortality rate was 4%, and significant morbidity occurred in 5% of patients. Significant indicators of poor outcome were worsened clinical grade, posterior aneurysm location, and large aneurysm size. CONCLUSION: Hypertensive patients, older patients, and patients with posterior circulation aneurysms had poorer neurologic status, which significantly influenced outcome. Larger aneurysms and vertebrobasilar aneurysms were associated with poor outcomes.

Adolescent↗

PubMed2003

Inhibition of apoptosis by hyperbaric oxygen in a rat focal cerebral ischemic model.

The hypothesis was tested that hyperbaric oxygen therapy (HBO) reduced brain infarction by preventing apoptotic death in ischemic cortex in a rat model of focal cerebral ischemia. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) and subsequently were exposed to HBO (2.5 atmospheres absolute) for 2 h, at 6 h after reperfusion. Rats were killed and brain samples were collected at 24, 48, 72 h, and 7 days after reperfusion. Neurologic deficits, infarction area, and apoptotic changes were evaluated by clinical scores, 2,3,7-triphenyltetrazolium chloride staining, caspase-3 expression, DNA fragmentation assay, and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL)-hematoxylin and eosin (H&E) costaining. In MCAO/R without HBO treatment animals, DNA fragmentation was observed in injured cortex at 24, 48, and 72 h but not in samples at 7 days after reperfusion. Double labeling of brain slides with NeuN and caspase-3 demonstrated neurons in the injured cortex labeled with caspase-3. TUNEL+H&E costaining revealed morphologic apoptotic changes at 24, 48, and 72 h after reperfusion. Hyperbaric oxygen therapy abolished DNA fragmentation and reduced the number of TUNEL-positive cells. Hyperbaric oxygen therapy reduced infarct area and improved neurologic scores at 7 days after reperfusion. One of the molecular mechanisms of HBO-induced brain protection is to prevent apoptosis, and this effect of HBO might preserve more brain tissues and promote neurologic functional recovery.

Animals↗