Risk factors of congenital hydrocephalus: a 10 year retrospective study.

OBJECTIVE: To evaluate and identify the risk factors associated with the pathogenesis of congenital hydrocephalus in a large specific population. METHODS: An International Classification of Diseases (ICD)-9 database search of patients with congenital hydrocephalus treated at the University of Mississippi Medical Center between 1998 and 2007 was performed. All recruited patients were interviewed, assessing maternal age, onset of prenatal care, geographic location of pregnancy, maternal diabetes and chronic hypertension, pregnancy induced hypertension, pre-eclampsia, eclampsia, single or multiparous gestation, maternal alcohol, tobacco and drug use, infection and trauma during gestation, trauma or sexually transmitted disease at parturition, and other family members with hydrocephalus. RESULTS: In this 10 year retrospective study, several significant risk factors were identified among 596 well defined cases of congenital hydrocephalus. The identified risk factors included lack of prenatal care, multiparous gestation, maternal diabetes, maternal chronic hypertension, maternal hypertension during gestation and alcohol use during pregnancy. Of these patients with congenital hydrocephalus, 12.1% identified an additional family member also diagnosed with hydrocephalus. No differences in risk factors were identified between sporadic and familial congenital hydrocephalus cases except for an increased incidence of multiparous pregnancies and prenatal care in the first trimester in familial cases. CONCLUSIONS: A number of key risk factors have been identified to be strongly associated with the development of congenital hydrocephalus in an infant. The prevalence of familial patterns of inheritance for congenital hydrocephalus suggests a broader role for genetic factors in the pathogenesis of congenital hydrocephalus.

The expression and activation of matrix metalloproteinase-1 after subarachnoid haemorrhage in rats.

BACKGROUND: Collagen lattice contraction has been reported as another aspect of the pathogenesis of cerebral vasospasm after subarachnoid haemorrhage (SAH). Recently, some authors have suggested that matrix metalloproteinase-1 (MMP-1) plays an important role in collagen lattice contraction. Therefore, this study aimed to clarify a role of MMP-1 during cerebral vasospasm in a rat SAH model. METHOD: We used a single-SAH model in rats and assessed the basilar arteries (BAs) at 30 minutes and on 2 days after SAH by cross-sectional area measurement and other histological parameters. Immunohistochemistry and Western blot analysis were used to quantify MMP-1 expression and activation. RESULTS: BAs in rats significantly exhibited severe cerebral vasospasm at 30 minutes after SAH and moderate vasospasm on Day 2. The immunohistochemistry and Western blotting performed in BAs of rats demonstrated that both expression and activation in MMP-1 peaked at 30 minutes after SAH and then declined to the control level. CONCLUSIONS: MMP-1 is expressed and activated in a parallel time course to the development of cerebral vasospasm in an experimental model of SAH.

Improved rat model for cerebral vasospasm studies.

While the rat has been used extensively in subarachnoid hemorrhage (SAH)-cerebral vasospasm studies, concerns exist whether this animal represents a usable model because its time course and pattern of cerebral vasospasm following SAH is not comparable to that observed in man. At present, our knowledge of the rat model is based almost exclusively on studies using a 'single hemorrhage' method. Since there is a positive correlation between severity of cerebral vasospasm, and volume of subarachnoid blood, an obvious question is whether the rat will show modifications in vascular responses when insulted by a second SAH. Here, an SAH was produced in rats using a 'double hemorrhage' method. Following SAH, cerebral arteries showed pathological alterations, significant decreases in luminal perimeter, and increases in arterial wall thickness, over a 7-day post-SAH period. The above vascular features are considered to be indicative of cerebral vasospasm and their presence over a 7-day post-SAH period represents a significant time extension when compared to a single hemorrhage. These modified vascular responses made the double hemorrhaged rat a much-improved animal model.

Age-related RhoA expression in blood vessels of rats.

Aging is a major risk factor for the development of vascular diseases that lead to stroke and heart failure. Several cellular factors such as cell adhesion, motility, contractile response, and cytokinesis are involved in the aging process. RhoA, a member of the Rho family, plays a primary role in the regulation of these cellular factors. This study aims to investigate whether RhoA is involved in these age-related responses to vascular change. We found that in older rats (19 months ole), RhoA mRNA increased 1.9-fold in the aortic arteries and 2.4-fold in the basilar arteries compared to the younger rats (2 months old). Membrane binding, but not cytosol RhoA, levels were found to significantly increase in the aortic and basilar arteries with age, which suggests that RhoA activity increases in older rats. Staining of RhoA increased markedly with age in both the medial and endothelial layers of the collected aortic and basilar arteries. These results show that RhoA expression and activity in the aortic and basilar arteries increased as a function of age, thereby suggesting that RhoA might be altered in the vascular response change of aged rats.

Caspase inhibitors attenuate oxyhemoglobin-induced apoptosis in endothelial cells.

BACKGROUND AND PURPOSE: Our recent study showed that oxyhemoglobin (OxyHb) induces apoptosis in cultured endothelial cells. Apoptosis requires the action of various classes of proteases, including a family of cysteine proteases known collectively as the caspases. This study was undertaken to investigate the effect of 2 caspase inhibitors, Z-VDVAD-FMK and Z-DEVD-FMK, in the protection of endothelial cells from OxyHb-induced apoptosis. METHODS: Cultured bovine brain microvascular endothelial cells (passages 5 to 9) were exposed to OxyHb (10 micromol/L) for 24 to 72 hours with and without caspase inhibitors. Cell attachment, DNA ladder, Western blotting of poly(ADP-ribose) polymerase (PARP), and caspase activities were measured to confirm the cytotoxic effect of OxyHb and the protective effect of the caspase inhibitors. RESULTS: (1) OxyHb produced cell detachment in a time-dependent manner. (2) OxyHb increased caspase-2 and -3 activities, produced DNA ladders, and cleaved PARP in endothelial cells. (3) Z-VDVAD-FMK and Z-DEVD-FMK (100 micromol/L) attenuated OxyHb-induced cell detachment, reduced caspase-2 and -3 activities, abolished OxyHb-induced DNA ladders, and prevented OxyHb-induced cleavage of PARP. CONCLUSIONS: OxyHb activates caspase-2 and -3 in cultured brain microvessel endothelial cells. Caspase inhibitors attenuated the cytotoxic effect of OxyHb.

Relaxant effect of U0126 in hemolysate-, oxyhemoglobin-, and bloody cerebrospinal fluid-induced contraction in rabbit basilar artery.

BACKGROUND AND PURPOSE: It has been suggested that mitogen-activated protein kinase (MAPK) is involved in cerebral vasospasm after subarachnoid hemorrhage. The present study was undertaken to explore the inhibitory effect of U0126, a novel MAPK inhibitor, in the contraction of the rabbit basilar artery by 3 spasmogens: hemolysate, oxyhemoglobin, and bloody cerebrospinal fluid (CSF) from patients with vasospasm. METHODS: The contraction and relaxation of rabbit basilar arteries were measured by isometric tension. MAPK immunoprecipitation was assessed by Western blot analysis. RESULTS: (1) Pretreatment of the rabbit basilar arteries with U0126 reduced contractions to hemolysate, oxyhemoglobin, or bloody CSF applied subsequently. (2) In the absence of endothelial cells, U0126 produced an inhibitory effect similar to the contractions induced by hemolysate, oxyhemoglobin, or bloody CSF. (3) U0126 relaxed the sustained contraction induced by hemolysate, oxyhemoglobin, or bloody CSF. (4) Hemolysate, oxyhemoglobin, and bloody CSF enhanced MAPK immunoprecipitation. (5) U0126 reduced MAPK immunoprecipitation induced by hemolysate, oxyhemoglobin, and bloody CSF. (6) Hemolysate, oxyhemoglobin, and bloody CSF significantly increased MAPK activity in the rabbit basilar artery. (7) U0126 abolished the effect of hemolysate, oxyhemoglobin, or bloody CSF on MAPK activation. CONCLUSIONS: This study demonstrated a role of MAPK in the contraction of rabbit basilar arteries by hemolysate, oxyhemoglobin, and bloody CSF. MAPK inhibitor U0126 may be useful in the treatment of cerebral vasospasm.

Role of calcium channels in oxyhemoglobin-induced apoptosis in endothelial cells.

OBJECT: Oxyhemoglobin (OxyHb) released from hemolysed erythrocytes has been considered to be responsible for cerebral vasospasm after subarachnoid hemorrhage. The authors previously reported that OxyHb produced apoptosis in cultured vascular endothelial cells. The change in intracellular Ca++ homeostasis was expected to be one of the possible mechanisms of the cytotoxic effects of OxyHb. This study was undertaken to investigate the protective effects of Ca++ channel blockers on OxyHb-induced apoptosis. METHODS: Cultured bovine coronary artery and brain microvascular endothelial cells (passages 5-9) were used. A cell density study, immunohistochemical staining, and DNA fragmentation analysis were performed to confirm apoptosis. Various concentrations (1-50 microM) of OxyHb were used for 24- to 72-hour incubations with and without Ca++-channel blockers. Oxyhemoglobin produced cytotoxicity leading to cell detachment from the culture dish in time- and concentration-dependent manners. The highest dose (50 microM) of OxyHb produced cell detachment after a 24-hour incubation, and the lower doses (1-10 microM) produced cell detachment after 48 to 72 hours. Immunohistochemical analysis showed that apoptosis occurred in cells that were still attached to the side of the culture dish after 48 to 72 hours of OxyHb treatment (5 microM). The OxyHb (10 microM) produced DNA ladders at 48 to 72 hours. Three Ca++-channel blockers were used to prevent the toxic effect of OxyHb. The voltage-dependent Ca++-channel blocker nicardipine (1 microM), the voltage-independent Ca++-channel blocker econazole (10 microM), and the inorganic Ca++-channel blocker lanthanum (100 microM) all failed to prevent cell detachment or DNA ladders produced by OxyHb. These results were similar in both cell lines. CONCLUSIONS: Oxyhemoglobin produced apoptotic changes in cultured vascular endothelial cells, and Ca++-channel blockers did not prevent OxyHb-induced apoptosis.

Upregulation of rho A and rho kinase messenger RNAs in the basilar artery of a rat model of subarachnoid hemorrhage.

OBJECT: Rho A, a small guanosine triphosphate-binding protein, and rho kinases have been suggested to play an important role in the agonist-induced myofilament Ca++ sensitization and cytoskeletal organization of smooth-muscle cells. To discover their possible roles in the prolonged contraction seen in cerebral vasospasm, the authors investigated the messenger (m)RNA expressions of rho A and rho-associated kinases alpha and beta in the basilar artery (BA) of a rat double cisternal blood-injection model. METHODS: An experimental subarachnoid hemorrhage (SAH) was achieved in rats by twice injecting autologous arterial blood into the cisterna magna of each animal. The mRNAs for rho A and rho-associated kinases alpha and beta of the rat BA were analyzed using reverse transcription-polymerase chain reaction (RT-PCR). The cisternal blood injection induced a marked corrugation of elastic lamina and contraction of smooth-muscle cells observed with the aid of light and transmission electron microscopy in the rat BA on Days 3, 5, and 7. Results of the RT-PCR revealed that mRNAs for rho A and rho kinases alpha and beta were expressed in the rat BA and that they were significantly upregulated and reached their peaks on Day 5. CONCLUSIONS: The mRNA upregulation of these proteins indicates that activation of rho A/rho kinase-related signal transduction pathways is involved in the development of long-lasting contraction of cerebral arteries after SAH.

Mechanism of ATP-induced [Ca(2+)](i) mobilization in rat basilar smooth muscle cells.

BACKGROUND AND PURPOSE: We have previously reported that extracellular ATP activates P(2u) receptors and increases intracellular free Ca(2+) ([Ca(2+)](i)) by G protein/phospholipase C/inositol 1,4,5-triphosphate pathways in cerebral artery smooth muscle cells. However, the possible contribution of other signaling pathways remains unclear. This study was undertaken to investigate the role of protein tyrosine kinase (PTK) and mitogen-activated protein kinase (MAPK) in mediating ATP-induced Ca(2+) mobilization in rat basilar artery smooth muscle cells (RBASMCs). METHODS: RBASMCs were freshly isolated, and [Ca(2+)](i) was monitored by fura 2 microfluorimetry. MAPK phosphorylation was studied by the Western blot technique. RESULTS: ATP produced a biphasic [Ca(2+)](i) response, which consists of releasing Ca(2+) from internal stores and influx from extracellular space. PTK inhibitors tyrphostin 51 and genistein inhibited [Ca(2+)](i) response to ATP. Tyrphostin A1, an inactive analogue of tyrphostins, failed to reduce the ATP-induced response. MAPK kinase inhibitor PD98059, but not U0126, reduced the ATP-induced [Ca(2+)](i) response. Phosphatidylinositol 3-kinase (PI3-K) tyrosine kinase inhibitor wortmannin, but not janus tyrosine kinase (JAK2) inhibitor AG490, partially inhibited the [Ca(2+)](i) response induced by ATP. In addition, ATP enhanced MAPK phosphorylation in a concentration- and time-dependent manner, and genistein, tyrphostin 51, PD98059, and U0126 inhibited MAPK phosphorylation. CONCLUSIONS: Extracellular ATP produced [Ca(2+)](i) elevation and MAPK phosphorylation in RBASMCs, and the effect was regulated by PTK. The role of MAPK in ATP-induced [Ca(2+)](i) elevation is not clear. PI3-K tyrosine kinase and JAK2 tyrosine kinase may not play an important role in the ATP-induced [Ca(2+)](i) response in RBASMCs.

Effect of endothelin receptor antagonists on non-muscle matrix compaction in a cell culture vasospasm model.

Endothelin-1 (ET-1), a potent vascular smooth muscle constrictor, is one of the possible spasmogens in cerebral vasospasm. However, the role of ET-1 in non-muscle compaction (another aspect of the pathogenesis of cerebral vasospasm) has not been reported. This study was undertaken to demonstrate the effect of ET-1, as well as erythrocyte lysate and bloody cerebrospinal fluid (CSF), on fibroblast populated collagen lattice (FPCL) compaction. Human dermal fibroblasts were used to form FPCL. The concentration-dependent effect of ET-1 was examined in the absence and presence of an ETA receptor antagonist (BQ-485), or an ETB receptor antagonist (BQ-788), or both. FPCL compaction was determined by measuring reduction of areas over five days following treatment. To compare the effect of ET-1 on lattice compaction, erythrocyte lysate and bloody CSF obtained from a cerebral vasospasm patient were also tested. We found that ET-1 increased FPCL compaction in a concentration-dependent (but not time-dependent) manner. Erythrocyte lysate produced the strongest compaction, however, without time-dependence. Bloody CSF promoted FPCL compaction in a time-dependent fashion. Compaction induced by ET-1 was inhibited by BQ-485 but not by BQ-788. We concluded that ET-1 promotes FPCL compaction by activation of ETA receptors. Other components in bloody CSF or erythrocytes may also contribute to FPCL compaction.

Apoptosis of endothelial cells in vessels affected by cerebral vasospasm.

BACKGROUND: Cerebral vasospasm after subarachnoid hemorrhage is a prolonged contraction that leads to cerebral ischemia or infarction. Morphological studies of cerebral arteries during vasospasm have shown extensive necrosis of smooth-muscle cells and desquamation and dystrophy of endothelial cells. The mechanism of cellular death is unknown. METHODS: We report an observation of apoptotic changes in the cerebral arteries of a patient who died after suffering severe cerebral vasospasm caused by aneurysmal rupture. Subarachnoid hemorrhage and cerebral vasospasm were confirmed by computed tomography scanning and angiogram. Histological and immunohistological examinations for apoptosis were performed in cerebral arteries. For control, the arteries from another patient, who died of trauma without head injury, were used. RESULTS: Corrugation of the internal elastic lamina and increased amounts of connective tissue was demonstrated by light microscopy. Apoptotic changes, characterized by condensation of chromatin of the nucleus and detachment from the basal membrane, were found on transmission electron microscopy in endothelial cells. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling reaction revealed positive staining of the nuclei of the endothelial cells. CONCLUSIONS: This study demonstrates that apoptosis occurred in the cerebral arteries in a patient who died of cerebral vasospasm. The possible role of apoptosis in cerebral vasospasm is discussed.

Risk factors for the development of post-traumatic cerebral vasospasm.

BACKGROUND: Post-traumatic vasospasm is a well-recognized sequela of head injury. The risk factors associated with post-traumatic vasospasm have not been well defined. We studied 119 consecutive patients with head injury to determine the risk factors for post-traumatic vasospasm. METHODS: Twenty-nine (27.1%) patients were excluded from the study because of poor insonation (n = 12) or a hospital stay of less than 72 hours (n = 17). Seventy (77.8%) of 90 patients suffered severe head injury. Sixteen (17.8%) patients sustained moderate head injury and four (4.4%) patients sustained mild head injury. All patients were monitored with transcranial Doppler (TCD) ultrasonography daily. RESULTS: Post-traumatic vasospasm was detected in 32 (35.6%) of 90 patients. Among these patients, 29 (90.6%) had severe head injury, and three (9.4%) had moderate head injury. None of the patients with mild head injury suffered post-traumatic vasospasm. In most cases, the onset of post-traumatic vasospasm began on the fifth day and lasted 1 to 9 days. In 8 (25%) patients, post-traumatic vasospasm began within the first three days of the head injury. Among 32 patients with post-traumatic vasospasm, 10 (31.2%) patients had mild vasospasm, 20 (65.5%) had moderate vasospasm, and 2 (6.3%) had severe post-traumatic vasospasm. Clinical deterioration was documented in two (2.5%) patients. CONCLUSIONS: Development of post-traumatic vasospasm correlated only with severe subarachnoid hemorrhage on initial computed tomographic scan. There was an increased incidence of post-traumatic vasospasm in patients with epidural hematomas, subdural hematomas, and intracerebral hemorrhages. The Glasgow Coma Scale (GCS) score on admission was inversely related to the development of post-traumatic vasospasm. In most cases, the period of vasospasm was short and clinical deterioration was rare. Probably, two varieties of post-traumatic vasospasm exist, one that lasts a shorter time and does not correlate with the presence of SAH, and a second that correlates with the presence of SAH, lasts longer, and resembles aneurysmal vasospasm.

Mechanism of endothelin-1-induced contraction in rabbit basilar artery.

BACKGROUND AND PURPOSE: Endothelin-1 (ET-1) is suggested to be a major cause of cerebral vasospasm after subarachnoid hemorrhage. However, the mechanism of ET-1-induced contraction in cerebral arteries remains unclear. This study was undertaken to demonstrate the possible role of protein tyrosine kinase (PTK), mitogen-activated protein kinase (MAPK), and protein kinase C (PKC) in ET-1-induced contraction. METHODS: PD-98059, damnacanthal, wortmannin, AG-490, genistein, calphostin C, and staurosporine were used to inhibit, or relax, the ET-1-induced contraction of basilar artery, studied with an isometric tension system. Immunoprecipitation of MAPK in ET-1-stimultated rings of basilar artery without or with the above inhibitors was studied with Western blot. RESULTS: (1) ET-1 produced concentration-dependent contraction and MAPK immunoprecipitation in rabbit basilar artery by activation of ET(A) but not ET(B) receptors. (2) MAPK inhibitors PD-98059 and U-0126 produced dose-dependent inhibition of ET-1-induced contraction. (3) The Src tyrosine kinase inhibitor damnacanthal, the phosphatidylinositol-3 kinase inhibitor wortmannin, and the Janus tyrosine kinase(2) inhibitor AG-490 abolished ET-1-induced contraction. (4) The PKC inhibitor staurosporine but not calphostin C abolished ET-1-induced contraction, and the PTK inhibitor genistein partially reduced ET-1-induced contraction. (5) In arteries precontracted by ET-1, PD-98059, U-0126, wortmannin, AG-490, genistein, and staurosporine produced concentration-dependent relaxation. (6) ET-1 induced a biphasic and time-dependent MAPK immunoprecipitation. (7) PD-98059, U-0126, genistein, AG-490, and damnacanthal, but not staurosporine or wortmannin, abolished the effect of ET-1 on MAPK immunoreactivity. CONCLUSIONS: This study demonstrated that MAPK may be involved in ET-1-induced contraction in rabbit basilar artery. MAPK is downstream of PTK, Src, and Janus tyrosine kinase pathways but may not be downstream of phosphatidylinositol-3 kinase pathways. The possible involvement of PKC in ET-1-induced contraction requires further investigation. Inhibition of these pathways may offer alternative treatment for ET-1-induced contraction and cerebral vasospasm.

Oxyhemoglobin produces necrosis in cultured smooth muscle cells.

OBJECT: Myonecrosis in the tunica media, which is defined morphologically, is one of the most striking alterations in the cerebral arterial wall following subarachnoid hemorrhage (SAH). In this study, oxyhemoglobin (OxyHb) was added to cultured rat aortic smooth muscle cells to determine the pattern of cell death by morphological and biochemical techniques. METHODS: Confluent rat aortic smooth muscle cells were treated with OxyHb in a concentration- and time-dependent manner. Cell density was assayed by counting the number of cells that attached to the culture dishes after exposed to OxyHb. To identify cell death pattern, DNA analysis, electron microscopy, and Western blotting using poly (ADP-ribose) polymerase (PARP) antibody were performed. CONCLUSIONS: OxyHb decreased cell density in a concentration- and time-dependent manner. DNA analysis showed a smear pattern characteristic of cell necrosis. Transmission electron microscopy demonstrated disintegration of cell membrane and destruction of cell organelles. No apoptotic changes, such as condensation of chromatin or apoptotic bodies were observed. Western blotting using PARP antibody revealed that 116 kDa PARP was not cleaved to 85 kDa, an apoptosis-related fragment. These results demonstrated morphologically and biochemically that OxyHb induced necrosis, not apoptosis, in cultured smooth muscle cells.

Mitogen-activated protein kinase plays an important role in hemolysate-induced contraction in rabbit basilar artery.

OBJECT: Mitogen-activated protein kinase (MAPK) is an important signaling factor in the vascular proliferation and contraction, the two features of cerebral vasospasm following subarachnoid hemorrhage. We studied the possible involvement of MAPK in hemolysate-induced signal transduction and contraction in rabbit basilar artery. METHODS: Isometric tension was used to record the contractile response of rabbit basilar artery to hemolysate. Western blots using antibodies for MAPK were conducted. 1) Hemolysate produced a concentration-dependent contraction of rabbit basilar artery. Pre-incubation of arteries with MAPK kinase inhibitor PD-98059 markedly reduced the contraction induced by hemolysate. PD-98059 also relaxed, in a concentration-dependent fashion, the sustained contraction induced by hemolysate (10%). 2) Hemolysate produced a time-dependent elevation of MAPK immunoreactivity in Western blot in rabbit basilar artery. MAPK was enhanced 3 min after hemolysate exposure and the effect reached maximum at 5 min. The immunoreactivity of MAPK decayed slowly with time, but the level of MAPK was still higher than the basal level even at two hours after exposure to hemolysate. 3) Pre-incubation of arteries with MAPK kinase inhibitor PD-98059 abolished the effect of hemolysate on MAPK immunoreactivity. CONCLUSION: Hemolysate produced contraction of rabbit basilar artery possibly by activation of MAPK. MAPK inhibitors may be useful in the treatment of cerebral vasospasm.

Morphological presentation of posttraumatic vasospasm.

Posttraumatic vasospasm is a well-recognized sequela of head injury. The risk factors associated with posttraumatic vasospasm have not been well defined. We studied 119 consecutive patients with head injury to determine the risk factors for posttraumatic vasospasm. Posttraumatic vasospasm was detected in 32 (35.6%) of 90 patients. Among these patients, 29 (90.6%) had severe head injury and 3 (9.4%) had moderate head injury. None of the patients with mild head injury suffered posttraumatic vasospasm. In most cases, the onset of posttraumatic vasospasm began on the fifth day and lasted 1 to 9 days. In 8 (25%) patients, posttraumatic vasospasm began within the first three days of the head injury. Clinical deterioration was documented in two (2.5%) patients. Morphologically, posttraumatic vasospasm resembled features of aneurysmal vasospasm. We found increased corrugation of the internal elastic lamina and increased amounts of connective tissue in the subendothelial layer. These findings showed that posttraumatic vasospasm, although clinically more mild, demonstrated the same morphological changes as did aneurysmal vasospasm.

Role of tyrosine kinase in fibroblast compaction and cerebral vasospasm.

Hemolysate, a proposed causative agent for cerebral vasospasm following subarachnoid hemorrhage, produces contraction of cerebral arteries by activation of tyrosine kinases. In addition, hemolysate accelerates fibroblast collagen compaction that could play a role in cerebral vasospasm. We studied the effect of hemolysate on tyrosine phosphorylation and fibroblast collagen compaction in cultured dog cerebral and human dermal fibroblasts using tyrosine kinase inhibitors and tyrosine antibodies (Western blot). 1) Hemolysate was found to enhance tyrosine phosphorylation of two proteins approximately 64 and 120 kDa. The effect of hemolysate was time- and concentration-dependent. 2) Two main components in hemolysate, oxyhemoglobin and adenosine triphosphate (ATP), produced similar results to that of hemolysate. 3) Tyrosine kinase inhibitor genistein and tyrphostin A51 (30 microM) markedly reduced the effect of hemolysate on tyrosine phosphorylation. 4) In another study, hemolysate increased fibroblast collagen compaction and the effect of hemolysate was reduced by genistein and tyrphostin A51. We conclude that hemolysate activates tyrosine kinase that may lead to acceleration of fibroblast compaction. This effect of hemolysate may contribute to cerebral vasospasm.

Endoscopic treatment of symptomatic septum pellucidum cysts: with some preliminary observations on the ultrastructure of the cyst wall: two technical case reports.

OBJECTIVE AND IMPORTANCE: We describe two patients with symptomatic septum pellucidum cysts managed by endoscopic fenestration. In each case, tissue from the cyst wall was studied to define the origin of the cyst wall and fluid. CLINICAL PRESENTATION: The patients, a 6-year-old boy and a 42-year-old man, each presented with headaches and a syncopal episode. Imaging studies demonstrated large septum pellucidum cysts with obstruction of the foramina of Monro. INTERVENTION: The patients underwent endoscopic transventricular cyst fenestration with a 4-mm steerable fiberscope. The fenestrations were created to allow communication with the right and left lateral ventricles. In one patient, adhesions between the cyst wall and the foramen of Monro were lysed with endoscopic monopolar cautery. Tissue from the cyst walls was removed for examination by electron microscopy. Postoperatively, the headaches and syncopal episodes resolved in both patients. CONCLUSION: Endoscopic fenestration of symptomatic septum pellucidum cysts produces immediate relief of the mass effect of the cyst and resolution of associated symptoms. Cannulation of the lateral ventricle before cyst fenestration prevents inadvertent injury to the fornices, thalamus, internal capsule, caudate nucleus, and septal and thalamostriate veins. The endoscopic approach allows the surgeon to ensure communication within the ventricular system, thus avoiding placement of a shunt. Preliminary ultrastructural analysis indicates that the cyst walls derive from the septum pellucidum rather than the choroid plexus or arachnoid. The cellular machinery necessary for fluid secretion was identified in some specimens.