Mel H. Epstein

N-Acetylcysteine Enhances Hippocampal Neuronal Survival After Transient Forebrain Ischemia in Rats

BACKGROUND AND PURPOSE Free radical scavengers enhance neuronal survival in some models of transient forebrain ischemia. Recent experiments have suggested that N-acetylcysteine prevents cellular injury after a reperfusion injury. No information is available regarding the neuroprotective potential of the free radical scavenger N-acetylcysteine after transient forebrain ischemia. In this study we evaluated the potential of N-acetylcysteine to improve hippocampal neuronal survival after transient forebrain ischemia in the rat. METHODS In series A and B, ventilated, paralyzed, normothermic rats had 10 minutes of transient forebrain ischemia induced by bilateral carotid occlusion with hypotension induced by blood withdrawal (mean arterial blood pressure, 45 mm Hg). In series A, animals were administered N-acetylcysteine (163 mg/kg) 30 minutes and 5 minutes before transient forebrain ischemia. In series B, N-acetylcysteine (326 mg/kg) was administered 15 minutes after transient forebrain ischemia. In series C, N-acetylcysteine (326 mg/kg) was administered 15 minutes after transient forebrain ischemia in animals with a mean arterial blood pressure of 30 mm Hg during transient forebrain ischemia. All series had normal control, sham, and vehicle treatment groups. In all series, the rats were allowed to recover and were killed at 7 days after ischemia. The effect of forebrain ischemia was assessed by evaluating the number of viable neurons at bregma sections -3.3, -3.8, and -4.3 of the CA1 region of the hippocampus. RESULTS The results demonstrated no physiological difference among the various treatment groups. There were no differences in the number of viable neurons between the transient forebrain ischemia with no treatment group and the vehicle (saline)-treated transient forebrain ischemic groups. Animals pretreated with N-acetylcysteine (mean number of neurons, 84 +/- 6) had a significant increase (P < .05) in neuronal survival compared with vehicle-treated animals (mean number of neurons, 43 +/- 4). Animals posttreated with N-acetylcysteine (mean number of neurons, 89 +/- 9) had a significant increase in neuronal survival compared with vehicle-treated animals (mean number of neurons, 7 +/- 1). However, N-acetylcysteine protection was only partial at 45 mm Hg and did not improve neuronal survival (mean number of neurons, 22 +/- 3) in animals with a more severe ischemic insult (mean arterial blood pressure, 30 mm Hg during transient forebrain ischemia) compared with vehicle-treated animals (mean number of neurons, 10 +/- 1). CONCLUSIONS N-Acetylcysteine partially improved neuronal survival when administered before or after ischemia following transient cerebral ischemia (mean arterial blood pressure, 45 mm Hg) but not with a more severe ischemic insult of 10 minutes of transient cerebral ischemia with a mean arterial blood pressure of 30 mm Hg.

Potassium Cotransport with Sodium and Chloride in the Choroid Plexus

Abstract: The effects of loop diuretics and ion substitution on the 2‐min uptake of K (86Rb as marker) were analyzed to obtain evidence for K cotransport with Na and Cl in the choroid plexus epithelium. The isolated plexuses, which were excised from lateral ventricles of adult rats, were bathed in artificial cerebrospinal fluid (aCSF). At concentrations of 10‐6 to 10‐4M, the specific cotransport inhibitors, bumetanide and piretanide, suppressed uptake of K in a dose‐dependent manner. Ouabain‐insensitive K uptake was stimulated by preincubating the choroid plexus in aCSF very low in [Na] and [K], then incubating it in much higher concentrations of these cations; bumetanide (10‐4M) blocked this stimulated uptake by 52%. Moreover, tissue preincubation in Na‐ or Cl‐free medium, followed by incubation with normal concentrations of both ions, stimulated the ouabain‐insensitive uptake of K from 15 (baseline) to 35 nmol/mg dry weight. This stimulation of K transport depended on the simultaneous presence of both Na and Cl in aCSF, and replacing either ion alone did not stimulate the ouabain‐insensitive K uptake. Collectively, these findings, together with those from a previous pharmacological study of 22Na and 36Cl transport, constitute strong evidence for the cotransport of Na, K, and Cl in rat choroid plexus.

The relation between vertebral endplate shape and lumbar disc herniations.

Study Design. Blinded review of selected and un-selected computed tomographic myelograms. Objective. To determine whether shape of the vertebral body endplate margins is a risk factor for the development of symptomatic lumbar disc herniations. The law of LaPlace for a fluid-filled tube suggests that anular tension could be related to endplate shape and a propensity for disc herniation. Summary of Background Data. It was hypothesized that the law of Laplace could apply to the lumbar spine because of to the cylindrical shape of the lumbar disc and its high water content in nonelderly individuals. It was further hypothesized that differences in the radius of the curvature could place stresses on the anulus that would make posterior disc herniations more likely with “rounder” endplates. Methods. Ninety-seven contrast computed tomography scans were reviewed at transitional L4–L5 and L5–S1 in patients under 60 years of age, without previous spine surgery and without spondylolisthesis. Determinations of disc herniations and measurements of endplates were performed by blinded observers. A ratio of these measurements was used to determine the relative circularity of the endplate. Height, weight, body mass index, and disc endplate size and shape were related to the presence of disc herniation. Results. By multiple logistic regression, only endplate shape was strongly related to disc herniations. Endplate area was a less significant factor in men. Conclusions. The shape of the vertebral body margin at the endplate is an important factor contributing to the development of disc herniations at L4–L5 and L5–S1.

Hydrocephalus decreases chloride efflux from the choroid plexus epithelium

To explore the novel concept of intrinsic brain regulation of the choroid plexus (CP), we studied the function of the CP exposed to increased intracranial pressure (ICP). The function of the CP was evaluated by in vitro chloride (Cl-) efflux from isolated CP 21 days after kaolin induced hydrocephalus. The Cl- efflux was significantly decreased in animals with elevated intracranial pressure (rate constant, K = 0.024 +/- 0.001 s-1) and enlarged ventricles (K = 0.023 +/- 0.001 s-1) compared to sham animals (K = 0.031 +/- 0.001 s-1). In contrast, the Cl- efflux of CP from animals with normal ICP and ventricular size did not differ from sham animals. These results illustrate the first demonstration of regulation of the CP epithelial function with elevated ICP; they also suggest a brain-CP regulatory mechanism that alters CP function.

The Role of Angiotensin II in the Regulation of Blood Flow to Choroid Plexuses and Cerebrospinal Fluid Formation in the Rat

The effect of peripherally administered angiotensin II (AII) on blood flow to choroid plexuses was examined in pentobarbital-anesthetized rats. The indicator fractionation method with 123I- or 125I-N-isopropyl-p-iodoamphetamine as the marker was employed to measure blood flow. Basal blood flow to choroid plexus of the lateral cerebral ventricle (LVCP) (3.19 ± 0.23 ml g−1 min−1) was lower than that to choroid plexuses of the third (3VCP) and fourth (4VCP) ventricles (3.90 ± 0.38 and 3.95 ± 0.36 ml g−1 min−1, respectively). The effect of AII on choroidal blood flow varied depending on peptide dose and anatomical location of the choroidal tissue. AII infused intravenously at rates of 30 and 50 ng kg−1 min−1 decreased blood flow to both LVCP and 4VCP by 12–20%. Both lower (10 ng kg−1 min−1) and higher (100 and 300 ng kg−1 min−1) AII doses did not alter blood flow to LVCP and 4VCP. Blood flow to the 3VCP was not affected by any dose of the peptide used. In comparison, blood flow to cerebral cortex increased by 33% during intravenous AII infusion at a rate of 300 ng kg−1 min−1. The choroidal blood flow-lowering effect of moderate AII doses was abolished by both AT1 (losartan) and AT2 (PD 123319) receptor subtype antagonists (3 mg kg−1 i.v.). To determine whether the hemodynamic changes observed in choroid plexuses with moderate AII doses influence CSF formation, the ventriculocisternal perfusion was performed in rats (under the experimental conditions described) with Blue Dextran 2000 as the indicator. CSF production was not altered during intravenous infusion of AII at a rate of 30 ng kg−1 min−1. It is suggested that CSF formation is maintained in pathophysiological situations accompanied by increased plasma AII levels, which implicates a potential role for AII in regulating ion and water balance in the CNS.

Intracranial and spinal meningiomas in patients with breast carcinoma: case reports

Breast carcinoma has a high predisposition to metastasize to the brain parenchyma or spinal epidural space with development of progressive neurological symptoms and signs and frequently death of the patient. We report 8 patients with known breast cancer who developed neurological symptoms attributable to an intracranial meningioma and 1 patient who developed spinal cord dysfunction resulting from a thoracic meningioma. The removal of the meningiomas resulted in return of normal neurological function in all patients. At follow-up, all our patients are alive without evidence of meningioma or breast carcinoma recurrence, except 1 patient who died of a metastatic malignant melanoma. This clinical association requires repeated emphasis because of the potential benefit in management of patients with suspected metastatic disease. We have reviewed and summarized the reported literature and added our 8 cases. The mean age of presentation before the second tumor was 6 years. Breast carcinoma was diagnosed first in 85% of cases. The clinical symptoms of the meningiomas were focal neurological signs in 50% of the patients, raised intracranial pressure in 40%, and a seizure in 10%.

AT1 receptor subtype mediates the inhibitory effect of central angiotensin II on cerebrospinal fluid formation in the rat

The effect of central administration of angiotensin II (AII) on cerebrospinal fluid (CSF) formation was studied in pentobarbital-anesthetized, artificially-ventilated rats. CSF production was measured by the ventriculocisternal perfusion method with Blue Dextran 2000 as the indicator. Baseline value of CSF production was 3.35 +/- 0.08 microliters/min. Intracerebroventricular (i.c.v.) infusion of AII at rates of 0.5 and 5 pg/min significantly lowered (P < 0.01) CSF formation by 23% and 16%, respectively. In comparison, high peptide doses (50 and 500 pg/min) did not alter this parameter. The inhibitory effect of low AII doses on CSF formation was blocked by the i.c.v. AT1 receptor subtype antagonists, losartan and SK&F 108566 (2.4 and 2.7 ng/min, respectively), but not by the AT2 receptor subtype-specific agent, PD 123319 (3.8 ng/min). Peptide AII antagonists, [Sar1,Ile8]AII (5 ng/min), which binds to both AT1 and AT2 receptors, had a similar effect to those of AT1-specific blockers. It is concluded that AII, by controlling CSF formation, may influence the water and electrolyte balance in the brain.

Distal anterior choroidal artery aneurysm : Intraoperative localization and treatment

Distal anterior choroidal artery aneurysms with intraventricular hemorrhage are rare and difficult to treat. We report the case of a 46-year-old woman with a left distal anterior choroidal artery aneurysm presenting as a typical subarachnoid hemorrhage from which she had no focal neurological signs. Because the aneurysm was located within the dominant deep temporal lobe, we used intraoperative computed tomography to guide a probe to the aneurysm to allow minimal dissection. This is the first report of a successfully treated distal anterior choroidal artery aneurysm. Reports of this unusual aneurysm and methods of approaching deep temporal lesions are reviewed.

Congenital anomaly of the second cervical vertebra predisposing to progressive cervical myelopathy. A case report.

The authors describe a previously unreported constellation of developmental anomallies of the C2 vertebra, which predisposed to the development of cervical myatopahty in a young patient. The embryology of the vertebral column is reviewed briefly, and the origin of each anomely of the C2 vertebra is traced to one of the two early stages in development as follows: 1) the formation of the moonchymal vertebra or 2) its induction to cartilage. This case amphasizes the Importance of congenital sian osis in the development of cervical myelopathy in young patients. The outcome is favorable when it is treated aggressively.

The association of normal-pressure hydrocephalus with obstructive sleep apnea

This report describes a 70-year-old man with obstructive sleep apnea who deteriorated rapidly when nasal continuous positive airway pressure was begun. The patient was found to have normal-pressure hydrocephalus, which was possibly exacerbated by the nasal continuous positive airway pressure. A review of the literature indicates several significant associations between apnea, normal-pressure hydrocephalus, and increased intracranial pressure and suggests that the association of obstructive sleep apnea and hydrocephalus might not be rare. Implications for diagnosis and treatment are discussed. (J Geriatr Psychiatry Neurol 1992;5:238–240).