Spinal epidural cavernous hemangioma: case report.

Pure epidural cavernous hemangiomas are quite rare. In this paper, a case of lumbar epidural cavernous hemangioma presenting as a lumbar radiculopathy is presented. The magnetic resonance imaging findings, differential diagnosis and therapy options of this rare case are discussed.

Postfusion pullout strength comparison of a novel pedicle screw with classical pedicle screws on synthetic foams.

Pullout is a very common failure mode on the use of pedicle screws. Numerous studies were completed to increase the pullout strength of pedicle screws especially for osteoporotic bones. In this study, a previously designed pedicle screw type was tested before and after fusion condition. Synthetic polyurethane foams were used in all tests. Three different grades of foams were used in tests to simulate severely osteoporotic, osteoporotic, and healthy bones. Test blocks were produced and characterized in our clinical biomechanics laboratory. Foaming of polyurethane was accepted as fusion process (bone in growth). Pedicle screw including radial holes (new design) was tested both before and after the fusion. It also exhibited remarkably higher pullout strength after fusion than before fusion and most of other alternatives stated in the literature. In total, 70% higher pullout strength was achieved with new design after fusion. On the other hand, new design did not dominate other alternatives when comparison was carried out on severely osteoporotic and healthy bones. To the knowledge of the authors, this is the first study investigating the postfusion properties on synthetic foams.

Design and biomechanical testing of pedicle screw for osteoporotic incidents.

In this study, geometrical features of pedicle screws have been modified and their performances are compared. Performance analysis has been made in terms of pull-out strength and torsional strength. The parameters investigated are core diameter, holes drilled normal to screw axis, angle between sequential holes and distance between holes. Three different core diameter have been studied, which are 4 mm (normal core diameter), 5 mm (medium core diameter) and 5.5 mm (high core diameter). Distance between sequential holes has been arranged such that there is either one hole per pitch or one hole per two pitches. Angle between sequential holes is either 90 degrees or 120 degrees. According to the test results, the screw, with medium core diameter (5 mm) containing one hole per two pitches with 90 degrees angle between sequential holes, has exhibited the optimum performance considering torsional strength and pull-out strength requirements. Its torsional strength is slightly higher than and, when Grade 40 polyurethane foam was used as bone simulating material, its pull-out strength is as good as, an undrilled normal core diameter screw, which is already being used in surgical operations. The fatigue performance of this best performed screw has also been found satisfactory according to the related standard. Its pull-out strength is also tested on a calf vertebra and a promising result has been obtained.

Exacerbated brain damage, edema and inflammation in type-2 diabetic mice subjected to focal ischemia.

One of the limiting factors in stroke therapeutic development is the use of animal models that do not well represent the underlying medical conditions of patients. In humans, diabetes increases the risk of stroke incidence as well as post-stroke mortality. To understand the mechanisms that render diabetics to increased brain damage, we evaluated the effect of transient middle cerebral artery occlusion in adult db/db mice. The db/db mouse is a model of type-2 diabetes with four times higher blood sugar than its normoglycemic genetic control(db/+ mouse). Following transient middle cerebral artery occlusion, the db/db mice showed significantly higher mortality, bigger infarcts, increased cerebral edema, worsened neurological status compared to db/+ mice. The db/db mice also showed significantly higher post-ischemic inflammatory markers (ICAM1(+) capillaries, extravasated macrophages/neutrophils and exacerbated proinflammatory gene expression) compared to db/+ mice. In addition, the post-ischemic neuroprotective heat-shock chaperone gene expression was curtailed in the db/db compared to db/+ mice.

Spinal extradural arachnoid cyst.

BACKGROUND CONTEXT: Spinal extradural arachnoid cysts are uncommon expanding lesions. Idiopathic arachnoid cysts are not associated with trauma or other inflammatory insults. If they enlarge, they usually present with progressive signs and symptoms of neural compression. PURPOSE: Total removal of the cyst and repair of the dural defect is the primary treatment for large thoracolumbar spinal extradural arachnoid cysts causing neurogenic claudication. Laminoplasty may prevent spinal deformities in long segmental involvement. STUDY DESIGN: A clinical case was performed. PATIENT SAMPLE: We report a case of 25-year-old man with 1-year history of progressive back pain radiating to both legs. His diagnosis was dorsal intraspinal extradural cystic lesion longing from the level of T11 to L2 on magnetic resonance imaging. OUTCOME MEASURES: The patient's pain levels were noted as he reported. Physiologic outcome was assessed on pre- and postoperative motor and sensory examination. METHODS: The patient underwent a T11-L2 laminotomy and radical cyst wall resection was performed. A small communication with the subarachnoid space was seen at the level of T12. It was sealed with tissue fibrinogen after repair with primary suture. Titanium miniplates were used for laminoplasty. RESULTS: Follow-up magnetic resonance imaging demonstrated cyst resolution, and neurologic examination revealed no sensory and motor deficit. CONCLUSION: Extradural arachnoid cysts are primarily treated with total removal of the cyst wall and closure of the dural defect. Surgical treatment is curative for this rare lesion.

Neuronal protective effects of focal ischemic pre- and/or postconditioning on the model of transient focal cerebral ischemia in rats.

We investigated the neuroprotective effects of pre- and postconditioning on infarct volume in the transient middle cerebral artery occlusion (MCAo) model in rats. Thirty-two male rats were divided into occlusion, preconditioning, postconditioning and both pre- and postconditioning groups. MCAo (120 minutes) was monitored with continuous cerebral tissue oxygen (O2) pressure (PtiO2). Pre-conditioning comprised 10 minutes of MCAo, 24 hours prior to the 120 minute MCAo. The postconditioning algorithm was 30 seconds of reperfusion followed by 30 seconds of MCAo. This cycle was repeated 3 times at the onset of reperfusion. Comparison of infarct volumes showed a significant difference between the conditioned groups and occlusion group. Although there was better protection in the preconditioning group compared with the other two conditioned groups, the results did not reach statistically significant levels. The results suggest that preconditioning, postconditioning and pre/post conditioning have protective effects on cerebral ischemia.

Gangliocytoma associated with focal cortical dysplasia in a young-adult: a case report.

Neoplasms and (non-neoplastic) focal dysplasias may coexist as a cause of seizures in both the developing and mature brain. Low grade neoplastic lesions (ganglioglioma/gangliocytoma) may present with seizures, and distinction of these lesions from focal cortial dysplasia is difficult on standard radiological imaging. We report a 24-year-old man who had complaints of tonic-clonic seizures for one week duration and was admitted to department of neurosurgery. He did not have any neurological deficit on his examination. Cranial computerized tomography and magnetic resonance imaging of the patient revealed a calcified, cystic lesion with contrast enhancement, in the left temporoparietal region. Subtotal resection of the mass was performed. Pathological examination revealed focal cortical dysplasia associated with gangliocytoma.

Transcription factor early growth response-1 induction mediates inflammatory gene expression and brain damage following transient focal ischemia.

Early growth response-1 (Egr1) is a sequence-specific transcription factor (TF) which is induced under hypoxic conditions. We presently report that transient middle cerebral artery occlusion (MCAO) leads to increased expression of Egr1 in the brains of adult mice and rats between 2 h and 5 days of reperfusion with a peak increase of 8-12-fold at 1 day. When subjected to transient MCAO and 3 days of reperfusion, Egr1-/- mice showed significantly smaller infarcts (by 44.9 +/- 8.4%, p < 0.05) and improved neurological function than Egr1+/+ littermates. Following transient MCAO, brains of Egr1-/- mice showed less water accumulation and decreased neutrophil infiltration (by 42 +/- 8%, p < 0.05) compared to Egr1+/+ mice. The number of activated microglia/macrophages were also significantly lower (OX42+ cells by 53 +/- 9%, p < 0.05 and ED1+ cells by 59 +/- 11%) in the post-ischemic cortex of Egr1-/- mice compared to Egr1+/+ mice. In addition, post-ischemic inflammatory gene expression was less pronounced in the brains of Egr1-/- mice compared to Egr1+/+ mice. Preventing cerebral Egr1 protein induction with small interference RNAs that target Egr1 decreased inflammatory gene expression and led to smaller infarcts (by 40.2 +/- 6.9%, p < 0.05) and reduced neurological deficits in rats subjected to transient MCAO. Conversely, transient MCAO following adenoviral-mediated Egr1 over-expression exacerbated the infarct volume (by 29 +/- 5.3%, p < 0.05) and worsened the neurological deficits in rats. These studies indicate Egr1 as a significant contributor of inflammation and neuronal damage after stroke.

Peroxisome proliferator-activated receptor-gamma agonists induce neuroprotection following transient focal ischemia in normotensive, normoglycemic as well as hypertensive and type-2 diabetic rodents.

Thiazolidinediones (TZDs) are synthetic agonists of the ligand-activated transcription factor peroxisome proliferator-activated receptor-gamma (PPARgamma). TZDs are known to curtail inflammation associated with peripheral organ ischemia. As inflammation precipitates the neuronal death after stroke, we tested the efficacy of TZDs in preventing brain damage following transient middle cerebral artery occlusion (MCAO) in adult rodents. As hypertension and diabetes complicate the stroke outcome, we also evaluated the efficacy of TZDs in hypertensive rats and type-2 diabetic mice subjected to transient MCAO. Pre-treatment as well as post-treatment with TZDs rosiglitazone and pioglitazone significantly decreased the infarct volume and neurological deficits in normotensive, normoglycemic, hypertensive and hyperglycemic rodents. Rosiglitazone neuroprotection was not enhanced by retinoic acid x receptor agonist 9-cis-retinoic acid, but was prevented by PPARgamma antagonist GW9662. Rosiglitazone significantly decreased the post-ischemic intercellular adhesion molecule-1 expression and extravasation of macrophages and neutrophils into brain. Rosiglitazone treatment curtailed the post-ischemic expression of the pro-inflammatory genes interleukin-1beta, interleukin-6, macrophage inflammatory protein-1alpha, monocyte chemoattractant protein-1, cyclooxygenase-2, inducible nitric oxide synthase, early growth response-1, CCAAT/enhancer binding protein-beta and nuclear factor-kappa B, and increased the expression of the anti-oxidant enzymes catalase and copper/zinc-superoxide dismutase. Rosiglitazone also increased the expression of the anti-inflammatory gene suppressor of cytokine signaling-3 and prevented the phosphorylation of the transcription factor signal transducer and activator of transcription-3 after focal ischemia. Thus, PPARgamma activation with TZDs might be a potent therapeutic option for preventing inflammation and neuronal damage after stroke with promise in diabetic and hypertensive subjects.

B1 and TRPV-1 receptor genes and their relationship to hyperalgesia following spinal cord injury.

STUDY DESIGN: Laboratory investigation of pain behavior following spinal cord injury. OBJECTIVE: To explore changes in the spinal cord expression of nociceptive genes following spinal cord injury (SCI) as they relate to the manifestation of pain behavior in rats. SUMMARY OF BACKGROUND DATA: Neuropathic pain following SCI is common, disabling, and largely untreatable. In peripheral nerve injury models, bradykinin B1 and vanilloid 1 (TRPV-1) receptor activity is associated with neuropathic pain behavior. We sought to examine the role of these gene products in SCI-mediated pain. METHODS: Rats were subjected to SCI using the MASCIS impactor. Animals were tested preinjury and at regular intervals postinjury for the appearance of thermal hyperalgesia using a hind limb withdrawal latency test. The expression of B1 and TRPV-1 genes was assessed using real-time polymerase chain reaction. Immunohistochemistry was used to localize the B1 and TRPV-1 receptors within the spinal cord. RESULTS: Greater than twofold increases in the expression of the B1 and TRPV-1 genes were detected in the injured region of the spinal cord in animals exhibiting hyperalgesia compared with animals with SCI that did not display hyperalgesia. Immunohistochemical staining revealed that both receptor types were largely localized to the dorsal horn. Staining for TRPV-1 receptors decreased while that for B1 receptors increased in all of the injured animals when compared with sham-operated controls. CONCLUSION: B1 and TRPV-1 receptor genes are overexpressed in the injured spinal cord of animals manifesting thermal hyperalgesia following SCI compared with similarly injured animals without hyperalgesia. This finding is consistent with past work regarding the role of these receptors in nociception and indicates that ongoing modifiable processes are occurring in the spinal cord that lead to clinical pain syndromes.

Decreased brain damage and curtailed inflammation in transcription factor CCAAT/enhancer binding protein beta knockout mice following transient focal cerebral ischemia.

CCAAT/enhancer binding protein beta (C/EBPbeta) is a leucine-zipper transcription factor that regulates cell growth and differentiation in mammals. Expression of many pro-inflammatory genes including the cytokine interleukin-6 is known to be controlled by C/EBPbeta. We report that focal cerebral ischemia induced by transient middle cerebral artery occlusion (MCAO) significantly increases C/EBPbeta gene expression in mouse brain at between 6 and 72 h of reperfusion. To understand the functional significance of C/EBPbeta in postischemic inflammation and brain damage, we induced transient MCAO in cohorts of adult C/EBPbeta null mice and their wild-type littermates. At 3 days of reperfusion following transient MCAO, C/EBPbeta null mice showed significantly smaller infarcts, reduced neurological deficits, decreased terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells, decreased intercellular adhesion molecule 1 (ICAM1) immunopositive vessels, decreased extravasated neutrophils and fewer activated microglia/macrophages, compared with their wild-type littermates. Furthermore, GeneChip analysis showed that postischemic induction of many transcripts known to promote inflammation and neuronal damage was less pronounced in the brains of C/EBPbeta-/- mice compared with C/EBPbeta+/+ mice. These results suggest a significant role for C/EBPbeta in postischemic inflammation and brain damage.

Increased angiogenesis and angiogenic gene expression in carotid artery plaques from symptomatic stroke patients.

OBJECTIVE: Carotid plaque rupture is one of the main causes of stroke by creating cerebral emboli. The biochemical, molecular, and structural factors that promote carotid plaque rupture are not yet understood in detail. We hypothesize that increased microvascular blood flow within a carotid plaque might fissure the plaque, elevate local pressure, and promote plaque rupture. The aim of this study is to determine the role of angiogenesis and angiogenesis-related gene expression in symptomatic carotid plaque. METHODS: The present study evaluated the new vessel formation (using hematoxylin-eosin staining and CD34 immunohistochemistry) and angiogenic gene expression (using microarray and real-time polymerase chain reaction analysis) in carotid plaque specimens obtained during endarterectomy from 13 symptomatic stroke patients in comparison with eight asymptomatic patients. RESULTS: Symptomatic plaques showed significantly higher new vessel density in the fibrous cap (by 347%, P < 0.05) as well as in the plaque proper (by 196%, P < 0.05) compared with the asymptomatic plaques. The fibrous caps of the plaques were threefold thinner in the symptomatic patients when compared with the asymptomatic patients. In symptomatic plaque, gene expression analysis showed increased abundance of 31 transcripts known to promote angiogenesis and cell division compared with plaques of asymptomatic patients. CONCLUSION: This study suggests that angiogenic gene expression and the ensuing angiogenesis in the plaques might contribute to their destabilization and resulting symptoms.

EGF and FGF-2 infusion increases post-ischemic neural progenitor cell proliferation in the adult rat brain.

OBJECTIVE: Epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2) play a critical role in neurogenesis. In the present study, we evaluated the additive effect of administering these two factors on post-ischemic progenitor cell proliferation, survival, and phenotypic maturation in the hippocampal dentate gyrus (DG) and the subventricular zone (SVZ) in the adult rat brain after transient middle cerebral artery occlusion. METHODS: A combination of EGF+FGF-2 (each 1.44 ng/d) was continuously administered into the lateral ventricles for 3 days, 5-bromodeoxyuridine (BrdUrd) was injected (50 mg/Kg) twice daily for 3 days starting on Day 1 of reperfusion, and cohorts of rats were sacrificed on Day 5 and Day 21 of reperfusion. RESULTS: Compared with sham controls, ischemic rats showed a significantly higher number of newly proliferated cells in both the DG (by 766 +/- 37%, P < 0.05) and the SVZ (by 650 +/- 43%, P < 0.05). Of the progenitor cells proliferated on Day 5 after ischemia, 41 +/- 6% in the DG and 28 +/- 5% in the SVZ survived to 3 weeks. Compared with vehicle control, the EGF + FGF-2 infusion significantly increased the post-ischemic progenitor cell proliferation (by 319 +/- 40%, P < 0.05 in the DG and by 366 +/- 32%, P < 0.05 in the SVZ) and survival (by 40 +/- 12%, P < 0.05 in the DG and by 522 +/- 47%, P < 0.05 in the SVZ) studied at 5 and 21 days, respectively. Furthermore, of the newly proliferated cells survived to 3 weeks after ischemia, EGF + FGF-2 infusion caused a significantly higher number of neuronal nuclear protein-BrdUrd double-positive mature neurons in the DG (46 +/- 9%, P < 0.05) compared with vehicle control. Neuronal nuclear protein and BrdUrd double-positive mature neurons were also found in the DG. Glial fibrillary acidic protein-positive astrocytes did not show double-positive staining in either region. CONCLUSION: Specific growth factor infusion enhances post-ischemic progenitor cell proliferation by 5 days of reperfusion and neuronal maturation by 21 days of reperfusion in both the DG and SVZ in the adult rat brain.

Cervical syringohydromyelia secondary to chronic supratentorial subdural hematoma.

INTRODUCTION: Syringohydromyelia associated with supratentorial space-occupying lesion has rarely been reported. We present a 28-year-old woman was admitted to the hospital with head and neck pain. Upon examination, there was only left central facial paralisia, with no evidence of papilledema. METHODS AND RESULTS: Cranial magnetic resonance imaging (MRI) revealed a left parietal and temporal chronic subdural hematoma (CSH) with a 1-cm shift to the right from midline. Also, cervical MRI revealed a syringohydromyelic cavity at the level of C6/7. The patient was operated on for supratentorial CSH. A follow-up cervical MRI revealed no syringohydromyelic cavity after 2 months. No neurological deficit was reported, and overall outcome was excellent. CONCLUSION: Syringohydromyelia was secondary to a space-occupying lesion in our case of supratentorial chronic subdural hematoma.

Ideal suture diameter is critical for consistent middle cerebral artery occlusion in mice.

OBJECTIVE: The use of transgenic and knockout mice has led to a need for a consistent model of mouse transient focal cerebral ischemia. In a great majority of the published mouse middle cerebral artery (MCA) occlusion studies, the methods indicated the type of intraluminal suture used without indicating the actual suture diameter after modification. We attempted to determine the ideal suture diameter to produce consistent occlusion in the MCA of adult male C57BL/6 mice. METHODS: Suture tips were coated to a depth 4 mm with glue, and 6-0 sutures of eight different, precisely measured diameters were produced. The coated 6-0 sutures in different diameters were introduced 10 mm into the internal carotid artery via the external carotid artery of the mice to produce MCA occlusion (n = 40; five animals for each diameter), and the mice (22-24 g) were transaortically perfused with saline. The base of the brain was exposed, and photographs of the vessels were obtained before and after transaortic injection of Evans blue dye to determine the consistency of MCA occlusion for each suture diameter. Cerebral blood flow was measured 10 minutes before occlusion and 20 minutes after reperfusion, and 2,3,5-triphenyltetrazolium chloride staining was performed to demonstrate the ischemic damage in additional animals with 110-microm (n = 5) and 180-microm (n = 8) diameter sutures. RESULTS: Sutures measuring 170 microm and 180 microm in diameter consistently occluded the MCA of C57BL/6 mice. In addition, 2,3,5-triphenyltetrazolium chloride staining demonstrated consistent infarction with 180-microm diameter sutures. The infarct volume was 36.3 +/- 4.2 mm3. CONCLUSION: Small changes in the diameter of the occlusion suture tip affect consistency in the mouse MCA occlusion model.

Single or multiple small subarachnoid hemorrhages by puncturing a small branch of the rat basilar artery causes chronic cerebral vasospasm.

OBJECTIVE: This study looked at the effects of single and multiple small subarachnoid hemorrhage (SAH) caused by puncturing a small branch of the basilar artery in rats. METHODS: Rats were subjected to single SAH (n = 21), multiple SAH (n = 21), sham operation (n = 21), or no procedures (control group, n = 7). SAH was induced in rats by transclival puncture of a small branch of the basilar artery. In the multiple-SAH hemorrhage groups, three small hemorrhages were produced in the same artery at three different times (initial and 24 and 48 h). In the single-SAH groups, one small hemorrhage was produced. Measurements of local cerebral blood flow (LCBF) were made at the initial SAH procedure and at three different time points. Seven animals from each general grouping were killed on Days 4, 10, and 14 (after LCBF was measured). Three different levels of the basilar artery were examined in each animal. Luminal area and arterial wall thickness were measured, and the findings were compared with control and corresponding sham group findings. RESULTS: LCBF dropped dramatically (by 40%) immediately after SAH and reached levels near baseline within 15 minutes (n = 42) (P < 0.001). LCBF continued to drop after initial SAH and reached the lowest level on Day 10 (P < 0.001) or Day 14 (P < 0.05). Significant luminal narrowing (P < 0.01) and thickening of the arterial wall (P < 0.01) were observed in both groups. CONCLUSION: Single or multiple small SAHs produced by puncturing the basilar artery in the rat cause similar acute and chronic cerebral vasospasm.

Transient focal cerebral ischemia-induced neurogenesis in the dentate gyrus of the adult mouse.

OBJECT: Throughout the life of a mammal, new neurons are produced each day from resident progenitor cells located in the hippocampal dentate gyrus (DG). The availability of transgenic and knockout mice enables the evaluation of specific molecular mediators of this phenomenon. To facilitate such studies the authors characterized the proliferation, survival, and maturation of progenitor cells in the DG of adult mice following transient focal cerebral ischemia. METHODS: Anesthesia was induced in adult C57BL/6 mice by administering halothane. The middle cerebral artery (MCA) was then occluded for 120 minutes by applying an endovascular suture. The marker used to detect the presence of proliferating cells, 5-bromodeoxyuridine (BrdU; 50 mg/kg) was administered intraperitoneally twice daily on Days 2 through 6 after the MCA occlusion. Cohorts of mice were killed on Days 7 and 21, after which their brains were sectioned and BrdU-positive cells were detected using immunohistochemical analysis. The phenotype of the BrdU-positive cells was identified by fluorescent triple labeling by using antibodies specific for neuronal and astroglial markers together with anti-BrdU antibodies. The infarction was confirmed by applying cresyl violet staining. Compared with sham-operated control animals, there was a 4.6-fold (p < 0.05) increase in BrdU-positive cells in the ipsilateral DG at Day 7 postischemia. Twenty-one percent of the newly proliferated cells survived to Day 21 postischemia. At this time, the newly proliferated cells expressed the immature and mature neuron markers doublecortin and NeuN, respectively, but none expressed the astroglial marker glial fibrillary acidic protein. CONCLUSIONS: Focal ischemia induces neurogenesis in the DG of the mouse brain; this may be critical for postischemic brain repair.

Infarct volume quantification in mouse focal cerebral ischemia: a comparison of triphenyltetrazolium chloride and cresyl violet staining techniques.

Triphenyltetrazolium chloride (TTC) and cresyl violet (CV) staining are routinely used methods to determine cerebral infarct volume and area. In this study, we compared these staining techniques using the mouse middle cerebral artery occlusion (MCAO) model of focal ischemia. Male C57BL6 mice were subjected to a 90 min transient MCAO and sacrificed at 24 h reperfusion. Sham operated mice served as controls. Two millimeters coronal brain slices were cut at +1.3, -0.7, -2.7 and -4.7 mm from bregma. The sections were stained with 2% TTC for 20 min and the caudal face of each slice was scanned with a flatbed scanner. The sections were kept in 4% paraformaldehyde solution for 4 weeks (the solution was changed every week). The slices were cryosectioned (40 microm thick), mounted on slides and stained with CV and scanned. The infarct volume and area were measured by the image-J program for both the staining techniques. There was no significant difference in either infarct area or volume between the TTC and CV stained sections (P > 0.05). TTC and CV staining showed a high degree of correlation in infarct area and volume indicating that both methods are suitable for producing accurate measurements of cerebral experimental infarcts.

Intracerebral hematoma after intranasal ethmoidectomy.

Intracerebral hematoma after an intranasal ethmoidectomy has been rarely reported in the literature. This 56-year-old man presented with postoperative confusion. The cause is local injury.

Stroke-induced progenitor cell proliferation in adult spontaneously hypertensive rat brain: effect of exogenous IGF-1 and GDNF.

Progenitor cells in the dentate gyrus of hippocampus (DG) and the subventricular zone of lateral ventricles (SVZ) generate new neurons throughout the life of mammals. Cerebral ischemia increases this basal progenitor cell proliferation. The present study evaluated the time frame of proliferation, length of survival and the phenotypes of the new cells formed after transient middle cerebral artery occlusion (MCAO) in adult spontaneously hypertensive rats. Compared to sham controls, ischemic rats showed a significantly higher number of newly proliferated cells (as defined by BrdU immunostaining) in both the DG (by fourfold, p < 0.05) and the SVZ (by twofold, p < 0.05). DG showed increased proliferation only in the first week of reperfusion and 49% of the cells formed in this period survived to the end of third week. Whereas, SVZ showed a continuous proliferation up to 3 weeks after MCAO, but the cells formed survived for less than a week. In both DG and SVZ, at the end of the first week of reperfusion, majority of the BrdU-positive (BrdU+) cells were immature neurons (DCX positive). In the DG, 28% of the cells formed in the first week after MCAO mature into neurons (NeuN positive). The ischemic cortex and striatum showed several BrdU+ cells which were ED-1 positive microglia/macrophages. At 1 week of reperfusion, MCAO-induced progenitor cell proliferation in the ipsilateral DG was significantly increased by i.c.v. infusion of IGF-1 (by 127 +/- 14%, p < 0.05) and GDNF (by 91 +/- 5%, p < 0.05), compared to vehicle. In the growth factor treated rats subjected to transient MCAO, several BrdU+ cells formed in the first week survived up to the third week.