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Biomedical subjects

S Nag

Publications and source records attributed to S Nag.

At least 73 records · Page 4Linked to original sources
PubMed1999

Remediation of attention deficits in head injury.

Head injury is associated with psychological sequelae which impair the patient's psychosocial functioning. Information processing, attention and memory deficits are seen in head injuries of all severity. We attempted to improve deficits of focused, sustained and divided attention. The principle of overlapping sources of attention resource pools was utilised in devising the remediation programme. Tasks used simple inexpensive materials. Four head injured young adult males with post concussion syndrome underwent the retraining program for one month. The patients had deficits of focused, sustained and divided attention parallel processing, serial processing, visual scanning, verbal learning and memory and working memory. After the retraining programme the deficits of attention improved in the four patients. Serial processing improved in two patients. Parallel processing and neuropsychological deficits did not improve in any patient. The symptom intensity reduced markedly and behavioural functioning improved in three of the four patients. The results supported an association between improving attention and reduction of symptom intensity. Attention remediation shows promise as a cost effective, time efficient and simple technique to improve the psychological and psychosocial functioning of the head injured patient.

Adult↗
PubMed1999

Standardization of creatine kinase-MB (CK-MB) mass assays: the use of recombinant CK-MB as a reference material.

BACKGROUND: The AACC assembled a committee to identify and validate a standard creatine kinase MB isoenzyme (CK-MB) material to improve the comparability of CK-MB mass assays. METHODS: Three protocols were used. In protocol I, various CK-MB materials prepared in different matrices were screened as candidate standards. In protocol II, participating manufacturers calibrated their systems with concentrates of human heart CK-MB and then tested 20 patient samples to evaluate calibration bias. In protocol III, participating manufacturers calibrated their immunoassay systems using recombinant CK-MB2 (rCK-MB2) diluted into their respective sample diluents and measured 50 samples. RESULTS: Candidate materials showed high recovery in stripped human serum, but bias improved only from 59% to 38%. These data led to the use of human heart CK-MB diluted in each manufacturer's sample diluent. This strategy reduced bias from 31% to 15%. Because human heart CK-MB is difficult to provide, a lyophilized source of CK-MB2 was identified. rCK-MB2 was shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, reversed-phase HPLC, intrinsic protein fluorescence, circular dichroism, agarose gel electrophoresis, immunoreactivity studies, high and low temperature stability, and reconstituted stability to be equivalent to human heart CK-MB. Calibration of immunoassay systems with rCK-MB2 added into each respective manufacturer's sample diluent showed a 13% between-manufacturer bias. CONCLUSION: Lyophilized rCK-MB2 was determined suitable for use as a reference material for CK-MB mass assays.

Calibration↗
PubMed1998

Intraoperative electron beam radiotherapy for previously irradiated advanced head and neck malignancies.

PURPOSE: This is a retrospective review to evaluate the role of surgery and intraoperative electron beam radiotherapy (IOERT) in the treatment of patients with previously irradiated advanced head and neck cancers. METHODS AND MATERIALS: Between January 1992 and March 1997, 38 patients (31 males, 7 females; median age of 62 years) with recurrent head and neck cancer were treated with maximal resection and IOERT at the Ohio State University (OSU). All had been previously treated with full-course radiotherapy (median 65.1 Gy, range 50-74.4 Gy). Twenty-nine patients (76%) had previously undergone one or more surgical procedures. After maximal surgery the tumor bed was treated with IOERT (single field in 36 patients and 2 fields in 2 patients), most commonly with 6 MeV electrons (87%). The dose administered (at 90% isodose line) was 15 Gy for close or microscopically positive margins in 34 patients and 20 Gy for gross disease in 1 patient. Further external beam radiation therapy (EBRT) was not given. RESULTS: After a median follow-up of 30 months (range 8-39 months), 24 of the 38 patients (66%) recurred within the IOERT field. Median time to IOERT failure was 6 months (95% CI: 4.3-7.7). The 6-month, 1-, and 2-year control rates within the IOERT volume were 41%, 19%, and 13%, respectively. Thirty of the 38 patients (79%) recurred in locoregional areas. Median time to locoregional failure was 4 months (95% CI: 3.3-4.7). The 6-month, 1-, and 2-year locoregional control rates were 33%, 11%, and 4%, respectively. Distant metastases occurred in 7 patients, 5 in association with IOERT failure and 2 with locoregional failure. Median overall survival was 7 months (95% CI: 4.7-9.3). The 6-month, 1-, 2-, and 3-year actuarial survival rates were 51%, 21%, 21%, and 8%, respectively. Major treatment-related complications occurred in 6 patients (16%). CONCLUSION: IOERT alone, at the dose used, is not sufficient for control of recurrent, previously irradiated head and neck cancers. Since higher IOERT doses are associated with high morbidity, we are currently evaluating the addition of limited EBRT dose and/or brachytherapy to improve the local control of these poor prognostic recurrent tumors, with acceptable morbidity.

Adenocarcinoma↗
PubMed1998

Vascular endothelial growth factor in Alzheimer's disease and experimental cerebral ischemia.

Several growth factors have been implicated in the pathogenesis of Alzheimer's disease (AD). We considered whether the vascular endothelial growth factor (VEGF) is involved in the vascular pathology associated with most cases of AD. We observed enhanced VEGF immunoreactivity in clusters of reactive astrocytes in the neocortex of subjects with AD compared to elderly controls. VEGF reactivity was also noted in walls of many large intraparenchymal vessels and diffuse perivascular deposits. In addition, we established that astrocytic and perivascular VEGF reactivity was enhanced in cerebral cortex of rats subjected to cerebral ischemia and to chronic hypoxia; experimental conditions known to be associated with astrogliosis and angiogenesis. We suggest the increased VEGF reactivity, also observed in infarcted human brain tissue, implicates compensatory mechanisms to counter insufficient vascularity or reduced perfusion (oligemia) apparent in AD.

Adult↗
PubMed1998

125Iodine brachytherapy for colorectal adenocarcinoma recurrent in the pelvis and paraortics.

PURPOSE: To evaluate the results of 125I brachytherapy in colorectal cancers recurrent in the pelvis and paraortics. METHODS AND MATERIALS: From September 1989 to January 1997, 29 patients with colorectal adenocarcinoma recurrent in the pelvis or the paraortic nodes were treated intraoperatively with permanent 125iodine seed implantation at the James Cancer Center of The Ohio State University (OSU). All patients had undergone prior surgery; 72% had prior EBRT. The implanted residual tumor volume was microscopic in 38% and gross in 62%. The implanted area (median 25 cc) received a median minimal peripheral dose of 140 Gy to total decay. An omental pedicle was used to minimize irradiation of the bowel. Five patients received additional postimplant EBRT (20-50 Gy; median 30 Gy). RESULTS: The 1-, 2-, and 4-year actuarial local-regional control rates were 38%, 17%, and 17%, respectively, with a median time to local failure of 11 months (95% CI 10-12 months). The first manifestation of disease progression in 52 % of the patients was local-regional. In addition, 22 patients (75%) developed distant metastases. The 1-, 2-, and 4-year actuarial overall survival rates were 70%, 35%, and 21%, (median = 18 months; 95% CI: 14-22 months). Overall survival was better for patients smaller volume implants (p = 0.007), with a lower total activity implanted (p = 0.0003), with a smaller number of implanted sites (p = 0.004), and with microscopic residual disease (p = 0.01). Patients receiving additional EBRT also had a better prognosis (p = 0.005). Local tumor progression was the cause of death in 34% of the patients who have died at the time of this report and 56% died of distant metastases. Of the patients, 13 (45%) experienced 15 toxic events, including 3 patients (10%) with enteric fistula. Neuropathy was not observed. CONCLUSIONS: 125I brachytherapy can be successfully used for salvage in patients with recurrent colorectal cancer. Patients with isolated, microscopic, or minimal gross residual disease requiring small-volume implants and those receiving additional EBRT have a better prognosis. Postimplant EBRT is now routinely added, even for previously irradiated patients, in an attempt to improve local control. Compared to IOERT and IOHDR, 125I brachytherapy is not associated with clinical neuropathy, probably due to the continuous low dose rate irradiation delivered by the 125I seeds.

Adult↗
PubMed1998

Cholinergic lesions of the rat brain by ibotenic acid and 192 IgG-saporin: effects on somatostatin, substance P and neuropeptide Y levels in the cerebral cortex and the hippocampus.

Impairment of the basal forebrain cholinergic system is an important change in the brains of Alzheimer's disease patients. Various neurotoxins have been used to achieve this in animal models. In this study the effects of chemical lesions by ibotenic acid (IBO), a glutamate analogue and by 192 IgG-saporin, a highly specific immunotoxin against cholinergic neurons, were investigated. The toxins were delivered stereotaxically into the brains of young Sprague-Dawley rats which were later sacrificed by decapitation. Choline acetyltransferase (ChAT) activity was measured by radioenzymatic assay and substance P (SP), neuropeptide Y (NPY) and somatostatin (SOM) levels by radioimmunoassay. Decreased ChAT and SOM levels were observed in the cortex and the hippocampus in both experiments. Cortical SP levels were increased after IBO lesions but were unaffected after 192 IgG-saporin lesions. NPY levels remained unchanged in both experiments. The results indicate that there were specific changes in neuropeptide contents in the cortex and hippocampus in response to cholinergic damage in the rat brain.

Alzheimer Disease↗
PubMed1998

The use of fluoroscopy to guide needle placement in interstitial gynecological brachytherapy.

PURPOSE: Interstitial brachytherapy is generally performed for gynecological malignancies with extensive parametrial involvement, by inserting the needles through a transperineal template. Often, the implanted needles are not parallel, and the multiple sources can be difficult to identify on localization radiographs, especially if obtained with a portable X-ray unit. We have used fluoroscopy to guide the needles for interstitial brachytherapy to treat various gynecological malignancies. Because the resultant needles are parallel, dosimetry can be performed based on the template hole positions used, rather than identifying individual sources. This report focuses on the technique; the outcome of patients implanted with this technique will be reported separately. METHODS: Seventy-one patients were implanted transperineally with 192iridium using a Syed template under fluoroscopic guidance, from September 1989 to May 1995, for bulky parametrial disease, narrow vagina, extensive vaginal involvement, recurrent disease after previous course of pelvic radiation therapy, or in cases in which the patient had previously undergone hysterectomy. 137Cesium was added in a central tandem in cases with a cervical os. Thirty patients were treated for primary cervical or vaginal carcinoma; 41 patients were treated for recurrent disease from endometrial or cervical cancers. The brachytherapy dose (prescribed to the periphery of the implant) was 40 to 55 Gy when used alone (15 patients) and 22-40 Gy when used as a boost to 34.2 to 59.4 Gy of pelvic external-beam radiotherapy (56 patients). The patients were followed for 6 to 63 months. RESULTS: In all cases, some of the needles had to be repositioned to improve the alignment. Hence, the use of fluoroscopy aided in achieving parallel placement of the needles in all implants as seen on anterior-posterior radiographs. Because the 192iridium sources were ordered beforehand based on the preplan, and the dosimetry was based on idealized geometry of the template hole positions, all patients were loaded on the same day of implant. CONCLUSION: Fluoroscopically guided perineal interstitial brachytherapy is a feasible technique for use in various gynecological malignancies. The use of fluoroscopic guidance helped to achieve parallel needle placement in all of our implants, but it required repositioning of some of the needles in all cases. The parallel positioning allowed the use of preplanned dosimetry, minimizing the delay in loading of the patients. The outcome of the patients treated using this technique is currently undergoing analysis and will be reported separately.

Brachytherapy↗
PubMed1998

Biliary tree malignancies.

Radiation therapy is used as definitive treatment for unresectable bile duct tumors, or as adjuvant therapy after resection. External beam irradiation of 45-50 Gy is generally given whenever feasible. Intraluminal brachy-therapy is a useful technique to deliver higher doses of radiation to the tumor while respecting the tolerance of the surrounding normal tissues. Brachytherapy can be given at a high dose rate or low dose rate via an in-dwelling biliary drainage catheter to boost external beam doses. Brachytherapy alone is reserved for palliative therapy. Techniques should be implemented with care to make them not only effective but safe. The long-term efficacy and morbidity of this mode of radiation should be studied further. Only large prospective trials can lead to resolution of some of the questions yet unsolved in treatment of these challenging malignancies.

Bile Duct Neoplasms↗
PubMed1998

Feasibility of intraoperative high-dose rate brachytherapy to boost low dose external beam radiation therapy to treat pediatric soft tissue sarcomas.

PURPOSE: To determine if a single intraoperative high-dose-rate brachytherapy (IOHDR) dose can be used in conjunction with low dose external beam radiation therapy (EBRT) to treat soft tissue malignancies in children with reduced morbidity. METHODS: From March 1992 to February 1995, six pediatric patients (4 boys, 2 girls; ages ranging from 4-13 years; median 10.5 years) were treated with IOHDR in conjunction with EBRT, chemotherapy, and radical surgery at nine sites not treatable by standard intraoperative electron beam radiation therapy techniques. The IOHDR dose was 10 Gy (at 7 sites with microscopic residual disease) or 12.5 Gy (at 2 sites with minimal gross residual disease) prescribed at 0.5 cm depth. The treatment volume varied from 9-96 cc (mean 30.3 cc). IOHDR was used in these patients because the tumor locations prevented positioning and insertion of conventional intraoperative electron beam applicators. The EBRT dose was limited to 27-30.6 Gy (median dose 27.4 Gy) postoperatively in all patients to minimize growth retardation or altered organ function. The median initial EBRT field size was 211 cm2 (range 25-483), with a median of two fields per patient (range 1-2). RESULTS: After a median follow-up of 40 months (range 22-62 months), all the patients were alive, five of them without evidence of disease. The other patient, with stage IV undifferentiated synovial sarcoma developed regrowth of pulmonary metastases at 14 months and local failure at 34 months. Toxicity was seen in two patients. One patient developed recurrent urinary infections and ureteral stenosis after 6 months and required a left nephrectomy. Another developed mild to moderate loss of visual acuity and impaired orbital growth after 6 months. CONCLUSIONS: Use of IOHDR in conjunction with low dose EBRT to obtain local control and long-term disease-free survival in pediatric soft tissue sarcomas is feasible with acceptable toxicity. Tumor beds not treatable with standard electron beam intraoperative radiation therapy could be satisfactorily encompassed with IOHDR.

Adolescent↗
PubMed1998

Interstitial brachytherapy in the management of primary carcinoma of the cervix and vagina.

PURPOSE: The purpose of this study was to determine the role of interstitial brachytherapy in the management of selected primary cancers of the cervix and the vagina. METHODS: Thirty-nine previously untreated patients with histologically confirmed carcinoma of the cervix (31 patients) and of the vagina (8 patients) were treated by a combination of external beam radiotherapy and fluoroscopic-guided interstitial brachytherapy between November 1989 and May 1995 at the Ohio State University Medical Center because they were not suitable for standard intracavitary brachytherapy. Clinical indications for interstitial brachytherapy were extensive parametrial involvement in 22 patients, extensive vaginal involvement in 10, and poor vaginal anatomy in 7. RESULTS: With a median follow-up of 36 months (range 12-66 months), 16 patients (51%) with cervical carcinomas and 5 patients (62.5%) with vaginal carcinomas have experienced local control of their tumor. The local control was better for tumors < 4 cm in largest diameter compared to tumors > 6 cm in largest diameter. The 5-year actuarial survival was 34 and 38% for cervical and vaginal cancers, respectively. Only 1 patient experienced grade 3 complications (2.5%). CONCLUSIONS: Interstitial brachytherapy can be safely used to treat patients unsuitable for standard intracavitary brachytherapy. When intracavitary dose distribution is expected to be suboptimal, interstitial brachytherapy is a good alternative.

Adenocarcinoma↗
PubMed1998

Simplified non-looping functional loop technique for HDR brachytherapy.

The loop technique has been employed in interstitial implantation of head and neck cancers for decades. However, cable-driven afterloading sources may be unable to negotiate the curve of the loop. The technique allows separate afterloading of each catheter ensuring a good dose distribution to the surface of the implanted structure.

Brachytherapy↗
PubMed1997

Pulmonary embolization of permanently implanted radioactive palladium-103 seeds for carcinoma of the prostate.

PURPOSE: It has been reported that permanently implanted iodine-125 seeds can embolize to the lungs. There is little data on the embolization of palladium-103 seeds. The purpose of this study is to collect and evaluate data on the embolization of Pd-103 seeds. METHODS AND MATERIALS: The records of 112 patients implanted with Pd-103 for carcinoma of the prostate were reviewed to systemically study the incidence and dynamics of pulmonary embolism of Pd-103 seeds. Five patients had no postoperative chest radiograph and were thus excluded, leaving 107 patients for review. RESULTS: Chest radiographs of 19 of the 107 patients showed embolized seeds in the lungs (18%). Two patients had three seeds each, nine patients had two seeds each; and in the remaining eight patients, a single seed migrated to the lungs. The seeds migrated mainly (84%) to the lower lobes. None of the eight patients who had their first postoperative chest radiograph on the day of the implant showed any embolized seeds. The embolized seed appeared only on subsequent chest radiographs taken 27 to 40 days later. Ten of the other 11 patients who had their first radiograph 1 to 97 days after brachytherapy had embolized seeds on their first chest radiograph. In the other patient, the embolized seed appeared only on a subsequent chest radiograph taken after 127 days. There were no clinical pulmonary or cardiac effects evident on routine follow-up of these patients with pulmonary embolized seeds. CONCLUSION: Embolization of Pd-103 seeds to the lungs after implantation for carcinoma of the prostate is an unusual event. In this study only 0.3% of the seeds implanted migrated to the lungs. Although it was previously thought that pulmonary seed migration mainly occurred on the day of brachytherapy, our experience shows that seeds usually migrated to the lungs after the day of the implant. There were no clinical pulmonary or cardiac effects attributable to embolized seeds in the lungs on routine follow-up.

Brachytherapy↗
PubMed1997

American Brachytherapy Society (ABS) consensus guidelines for brachytherapy of esophageal cancer. Clinical Research Committee, American Brachytherapy Society, Philadelphia, PA.

INTRODUCTION: There is wide variation in the indications, treatment regimens, and dosimetry for brachytherapy in the treatment of cancer of the esophagus. No guidelines for optimal therapy currently exist. METHODS AND MATERIALS: Utilizing published reports and clinical experience, representatives of the Clinical Research Committee of the American Brachytherapy Society (ABS) formulated guidelines for brachytherapy in esophageal cancer. RESULTS: Recommendations were made for brachytherapy in the definitive and palliative treatment of esophageal cancer. (A) Definitive treatment: Good candidates for brachytherapy include patients with unifocal thoracic adeno- or squamous cancers < or = 10 cm in length, with no evidence of intra-abdominal or metastatic disease. Contraindications include tracheal or bronchial involvement, cervical esophagus location, or stenosis that cannot be bypassed. The esophageal brachytherapy applicator should have an external diameter of 6-10 mm. If 5FU-based chemotherapy and 45-50-Gy external beam are used, recommended brachytherapy is either: (i) HDR 10 Gy in two weekly fractions of 5 Gy each; or (ii) LDR 20 Gy in a single course at 0.4-1 Gy/hr. All doses are specified 1 cm from the midsource or mid-dwell position. Brachytherapy should follow external beam radiation therapy and should not be given concurrently with chemotherapy. (B) Palliative treatment: Patients with adeno- or squamous cancers of the thoracic esophagus with distant metastases or unresectable local disease progression/recurrence after definitive radiation treatment should be considered for brachytherapy with palliative intent. After limited dose (30 Gy) EBRT, the recommended brachytherapy is either: (i) HDR 10-14 Gy in one or two fractions; or (ii) LDR 20-25 Gy in a single course at 0.4-1 Gy/hr. The need for external beam radiation in newly diagnosed patients with a life expectancy of less than 3 months is controversial. In these cases, HDR of 15-20 Gy in two to four fractions or LDR of 25-40 Gy at 0.4-1 Gy/hr may be of benefit. CONCLUSION: ABS guidelines for esophageal brachytherapy now exist and will be updated by the ABS in the future, as clinical data using more uniform treatment techniques becomes available.

Adenocarcinoma↗
PubMed1997

Intensified regimen for advanced head and neck squamous cell carcinomas.

OBJECTIVE: To devise an intensified treatment regimen for patients with advanced, resectable head and neck squamous cell carcinomas. DESIGN: Phase I/II clinical trial consisting of perioperative cisplatin chemoradiotherapy, surgical resection, intraoperative radiotherapy, and postoperative cisplatin chemoradiotherapy. SETTING: The Ohio State University Comprehensive Cancer Center, Columbus. PATIENTS: Thirty-seven patients (median age, 63 years) with advanced oral cavity, oropharyngeal, or hypopharyngeal carcinomas. RESULTS: The range of time at risk was 1 to 30 months (median, 21 months). Thirty of the 37 registered patients were analyzable; 11 have died (5 with distant metastases; 1 of lung carcinoma; and 5 were cancer-free); 2 experienced second primary tumors in the oral cavity (out of or adjacent to the previous radiotherapy portals). Treatment compliance was excellent (92%), morbidity was low, and excellent locoregional control was achieved. CONCLUSIONS: The initial results are encouraging; the future strategy will intensify the systemic component of therapy based on results from concurrent laboratory studies.

Antineoplastic Agents↗
PubMed1997

Perineal template interstitial brachytherapy salvage for recurrent endometrial adenocarcinoma metastatic to the vagina.

PURPOSE: To evaluate the use of interstitial brachytherapy salvage of recurrent endometrial adenocarcinoma metastatic to the vagina. METHODS: From September 1989 to February 1995, 15 patients with locally recurrent endometrial adenocarcinoma were treated with perineal template interstitial irradiation with low-dose-rate brachytherapy 192Ir/137Cs. Five of the 7 previously unirradiated patients received pelvic external beam radiation therapy (EBRT) of 45-50 Gy, with standard fractionation followed by an interstitial brachytherapy boost dose of 30 Gy (range 25 to 35 Gy). The other 2 patients received only brachytherapy of 40 Gy (palliative) and 50 Gy. Eight previously irradiated patients received only brachytherapy of 50 to 55 Gy. RESULTS: After a median follow-up of 47 months (range 14-81), the actuarial local control rate was 66.6%. The local control rate for patients treated with interstitial irradiation only was 64.3% and the local control rate for patients treated with interstitial irradiation + EBRT was 100%. Distant metastases occurred in 30.7% of the patients. Actuarial overall and disease-specific 5-year survival were 42.3 and 67.5%, respectively. Toxicity has been minimal, with 6 patients complaining of vaginal/rectal (RTOG) grade 1-3 complications (5 patients grade 1-2, 1 patient grade 3). CONCLUSIONS: These results suggest that perineal template interstitial irradiation (if possible with supplementary EBRT) is an effective alternative to radical or exenterative pelvic surgery for locally recurrent endometrial cancer. Excellent survival and local control rates can be achieved with low morbidity, especially if EBRT is added.

Adenocarcinoma↗
PubMed1997

A rare form of adult onset leukodystrophy: orthochromatic leukodystrophy with pigmented glia.

BACKGROUND: Orthochromatic leukodystrophy with pigmented glia and scavenger cells is a rare leukodystrophy of unknown etiology. This report describes a 42-year-old man with a history of depression, dementia and parkinsonism having the pathological features of orthochromatic leukodystrophy with pigmented glia. METHODS: We reviewed the clinical history and pathology of autopsy and brain biopsy material. RESULTS: Imaging revealed bilateral cerebral white matter hypodensities. At autopsy, the brain demonstrated a leukodystrophy affecting predominantly the cerebral hemispheres and characterized by demyelination, and cytoplasmic pigment deposits in oligodendroglia and astrocytes. The pigment had the staining properties of ceroid-lipofuschin and on ultrastructural examination was composed of membrane-bound lipid and electron-dense inclusions which had a fingerprint-like pattern. Similar pigment inclusions were not observed on ultrastructural examination of renal, splenic or hepatic tissue obtained at autopsy. The brain biopsy contained cerebral cortex with sparse subcortical white matter in which a few oligodendroglia and fewer astrocytes at the grey/white junctions showed cytoplasmic pigmentary inclusions identical to those described above. However, due to the paucity of white matter in the specimen a definite diagnosis of orthochromatic leukodystrophy with pigmented glia was not made. CONCLUSIONS: The diagnosis of orthochromatic leukodystrophy with pigmented glia and scavenger cells can only be made antemortem if the brain biopsy contains adequate white matter and although a rare condition, it should be considered in the differential diagnosis of an adult onset leukodystrophy.

Adult↗
PubMed1997

Role of vascular endothelial growth factor in blood-brain barrier breakdown and angiogenesis in brain trauma.

The role of vascular endothelial growth factor (VEGF) in blood-brain barrier (BBB) breakdown and angiogenesis, observed previously in the cerebral cortical cold-injury model, was investigated. Immunohistochemistry was used to assess BBB permeability to plasma fibronectin and to localize VEGF protein in the cortical cold-injury model over a period of 10 min to 14 days post-injury. BBB breakdown to fibronectin in lesion vessels was observed at 10 min post-injury, was maximal between 2 and 4 days and declined gradually thereafter, while occasional perilesional vessels remained permeable up to 6 days. Increased VEGF immunoreactivtiy occurred later-it was observed in pial vessels after 6 hours (h), and persisted up to day 14. Arterioles within the cold lesion showed VEGF immunoreactivity at 36 h, thus preceding the onset of endothelial proliferation and angiogenesis that occurred from day 3 to day 5. VEGF immunoreactivity was also observed in inflammatory cells and astrocytes. These results indicate that the immediate breakdown of the BBB in the cold lesion is unrelated to VEGF. The presence of mural VEGF in permeable pial vessels and lesional arterioles suggests that VEGF is one of several factors that mediates BBB breakdown in this model. The association of maximal VEGF immunoreactivity with endothelial proliferation and neovascularization suggests that VEGF promotes angiogenesis and repair following brain trauma.

Animals↗