We have examined the incidence and size of infarction after occlusion of different portions of the rat middle cerebral artery (MCA) in order to define the reliability and predictability of this model of brain ischemia. We developed a neurologic examination and have correlated changes in neurologic status with the size and location of areas of infarction. The MCA was surgically occluded at different sites in six groups of normal rats. After 24 hr, rats were evaluated for the extent of neurologic deficits and graded as having severe, moderate, or no deficit using a new examination developed for this model. After rats were sacrificed the incidence of infarction was determined at histologic examination. In a subset of rats, the size of the area of infarction was measured as a percent of the area of a standard coronal section. Focal (1-2 mm) occlusion of the MCA at its origin, at the olfactory tract, or lateral to the inferior cerebral vein produced infarction in 13%, 67%, and 0% of rats, respectively (N = 38) and produced variable neurologic deficits. However, more extensive (3 or 6 mm) occlusion of the MCA beginning proximal to the olfactory tract--thus isolating lenticulostriate end-arteries from the proximal and distal supply--produced infarctions of uniform size, location, and with severe neurologic deficit (Grade 2) in 100% of rats (N = 17). Neurologic deficit correlated significantly with the size of the infarcted area (Grade 2, N = 17, 28 +/- 5% infarction; Grade 1, N = 5, 19 +/- 5%; Grade 0, N = 3, 10 +/- 2%; p less than 0.05). We have characterized precise anatomical sites of the MCA that when surgically occluded reliably produce uniform cerebral infarction in rats, and have developed a neurologic grading system that can be used to evaluate the effects of cerebral ischemia rapidly and accurately. The model will be useful for experimental assessment of new therapies for irreversible cerebral ischemia.

https://www.ahajournals.org/doi/pdf/10.1161/01.STR.17.3.472

Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination.

Part two of this three-part series commences with anomalous dominance and special talents. Part one appears in a previous issue of theArchives. 1 ANOMALOUS DOMINANCE AND SPECIAL TALENTS According to our hypothesis, slowed growth within certain zones of the left hemisphere is likely to result in enlargement of other cortical regions, in particular, the homologous contralateral area, but also adjacent unfaffected regions. The influences that favor anomalous dominance may thus favor talents associated with superior development of certain regions either in the right hemisphere or in adjacent parts of the left hemisphere. Even with excessive retardation of growth and the resultant migration abnormalities and learning disorders (LD), high talents may exist as a result of compensatory enlargement of other cortical regions. Several types of data are in concordance with these conclusions. Several studies have claimed that the average level of spatial talents is higher in male subiects. 2 Hier

https://jamanetwork.com/journals/jamaneurology/articlepdf/584161/archneur_42_5_008.pdf

Cerebral lateralization. Biological mechanisms, associations, and pathology: II. A hypothesis and a program for research.

All cells in living organisms have a limited life span, and when the time set by their biological clocks has run out, they will die , their highly orga­ nized macromolec ular structure will disintegrate, and the low-molec ul ar degrad ation products be­ come part of the disorder of the surroundings . In thermodynamic terms, this series of events consti­ tutes what has been c alled the entropic doom. We know little about those molec ul ar mechanisms that limit the life span of cells in the absence of dise ase. For the clinician, therefore, the important task is to prevent or tre at dise ases that jeopardize the proper functioning and viability of cells whose biologic al clocks have not yet run out . Measures instituted to prevent brain cell death have a special importance . This i s partly due t o the fact that w e equate human life with the functioning of the brain. However, this importance also resides in the v ulnerability of brain cells to conditions that allow cells of most other tissue to survive , and to continue or res ume their activitie s . The clinically most important conditions leading to brain cell death are those associated with cere­ brovascul ar dise ase, particularly stroke, and with head trauma. We will begin, though, by rec alling the traditional view of the occ urrence and loc alization of neuronal damage in four conditions that lead to more disseminated alterations, e specially since they have been considered to c ause nerve cell injury of a

https://journals.sagepub.com/doi/pdf/10.1038/jcbfm.1981.18

Cell Damage in the Brain: A Speculative Synthesis

(2) peculiar "taming" effect on monkeys in that aggression disappears, and (3) thalamic stimulation.2 Although the drug has been in clinical use since 1954, reports of toxicity have been scattered, and only one review of adverse responses has appeared.3 One death has been reported.4 The purpose of this communication is to present a case of meprobamate idiosyncrasy with skin bi¬ opsy and skin testing, to review the pub¬ lished reports to date, and to discuss possible etiologic factors in the pathogene¬ sis of the anaphylactoid reaction. The records of more than 6500 patients have been summarized to date.8"81 Twentythree cases of attempted suicide,6"19 and one hundred thirteen cases of idiosyncrasy have

Report of a Case and Review of the Literature

We studied the response of cerebral blood flow to acute step decreases in arterial blood pressure noninvasively and nonpharmacologically in 10 normal volunteers during normocapnia, hypocapnia, and hypercapnia. The step (approximately 20 mm Hg) was induced by rapidly deflating thigh blood pressure cuffs following a 2-minute inflation above systolic blood pressure. Instantaneous arterial blood pressure was measured by a new servo-cuff method, and cerebral blood flow changes were assessed by transcranial Doppler recording of middle cerebral artery blood flow velocity. In hypocapnia, full restoration of blood flow to the pretest level was seen as early as 4.1 seconds after the step decrease in blood pressure, while the response was slower in normocapnia and hypercapnia. The time course of cerebrovascular resistance was calculated from blood pressure and blood flow recordings, and rate of regulation was determined as the normalized change in cerebrovascular resistance per second during 2.5 seconds just after the step decrease in blood pressure. The reference for normalization was the calculated change in cerebrovascular resistance that would have nullified the effects of the step decrease in arterial blood pressure on cerebral blood flow. The rate of regulation was 0.38, 0.20, and 0.11/sec in hypocapnia, normocapnia, and hypercapnia, respectively. There was a highly significant inverse relation between rate of regulation and PaCO2 (p less than 0.001), indicating that the response rate of cerebral autoregulation in awake normal humans is profoundly dependent on vascular tone.

Cerebral autoregulation dynamics in humans.

Stiffness and elastic behavior of human intracranial and extracranial arteries.

The predilection sites of cerebrovascular lesions (cerebral hemorrhage and/or softening) were studied in 1,278 stroke-prone spontaneously hypertensive rats (SHRSP). The precise supply to the main cerebral arteries was determined by trypan blue injections and microangiography. The three major territories were the anteromedial cortex, the occipital cortex, and the basal ganglia. A common angioarchitectural characteristic of these three areas was the blood supply through "recurrent branching" from the main stream. In the basal ganglia, where there is a preponderance of lesions, the arteries responsible for these lesions belonged to the lateral group of lenticulostriate arteries. The primary pre-stroke arterial lesions were further studied microangiographically in SHRSP killed at the time the initial symptoms of stroke were detected. These points were located at the "boundary zone" of the main cerebral arteries. Our findings indicated the importance of these two angioarchitectural minor loci as the basis for functional or organic circulatory disturbances that may cause stroke. Since these local factors of stroke are common in the cortex and basal ganglia of rats and basal ganglia of humans, these SHRSP are regarded as good pathogenetic models for studies on stroke in humans.

Pathogenetic similarity of strokes in stroke-prone spontaneously hypertensive rats and humans.

Experimentally induced cerebral aneurysms in rats: Part V. Relation of hemodynamics in the circle of Willis to formation of aneurysms.

A randomized clinical study of irradiation and irradiation combined with ACNU in the treatment of malignant gliomas was performed in order to determine if there was an enhancing therapeutic effect of ACNU given in addition to radiotherapy. An effect was defined as a reduction in tumor size, changes in neurological signs and performance status within 1 month after the completion of radiotherapy, or statistically improved survival times. Seventy-seven patients from 14 neurosurgical clinics were included in this validated study group. Radiotherapy with a total dose of 5000 to 6000 rads, given in 25 to 30 subdoses, was applied to the whole brain and to a generous field surrounding the tumor. Patients who were assigned to receive chemotherapy were given ACNU intravenously once or twice during radiotherapy at a dose of 100 mg/sq m of body surface area. The response rate (more than 50% reduction of the tumor size) was 13.5% in the group treated by radiotherapy alone and 47.5% in the group with radiotherapy and ACNU. The hematological toxicity was more severe in the group treated with radiotherapy and ACNU. Other toxicity was mild and acceptable. The survival rates of patients with astrocytoma grade III and glioblastoma multiforme at 36 months after the surgery were 48.9% and 0% for radiotherapy alone and 59.0% and 16.3% for radiotherapy plus ACNU, respectively. The differences between the survival curves were not significant at the p = 0.05 level. This study has demonstrated that, although the use of ACNU during radiotherapy suppressed malignant gliomas more than radiotherapy alone, the survival time was not extended significantly. It is necessary to continue to search for an effective chemotherapeutic regimen to prolong survival of patients with malignant gliomas.

Effects of ACNU and radiotherapy on malignant glioma

✓The authors review 30 documented cases of intracranial and orbital cavernous angiomas treated at their institution between 1965 and 1984. The diagnosis was based on computerized tomography (CT) or surgery; three patients were treated in the pre-CT era (1965 to 1976) and 27 since the advent of CT. The number of cases diagnosed preoperatively markedly increased after the introduction of CT, and 22 cases were verified histopathologically at surgery. Six cases were in children (aged 2 months to 17 years) and 24 in adults (aged 19 to 73 years). There was no significant sex difference (male:female ratio was 14:16). Nineteen lesions were intraparenchymal, five were intraventricular, three were in the middle fossa, two were intraorbital, and one originated from the tentorium. Symptoms varied according to the site of the lesion; hemorrhage occurred in 11 cases. Calcifications were seen on CT scans in all cases, but on plain skull films in only two. Angiography revealed hypovascular masses in all cases excluding t...

Hajime Handa

Papers

Stiffness and elastic behavior of human intracranial and extracranial arteries.

Pathogenetic similarity of strokes in stroke-prone spontaneously hypertensive rats and humans.

Experimentally induced cerebral aneurysms in rats: Part V. Relation of hemodynamics in the circle of Willis to formation of aneurysms.

Effects of ACNU and radiotherapy on malignant glioma

Intracranial and orbital cavernous angiomas. A review of 30 cases.