Pattern Of Brain Damage Research Articles

Alcohol consumption and premature aging. A critical review.

Research conducted during the past ten years has demonstrated that alcoholics resemble yet older nonalcoholics on a variety of behavioral, radiological, electrophysiological, and regional blood flow measures of brain function. These similarities have led to speculation that excessive alcohol consumption causes a premature aging of the brain that, in turn, is responsible for the characteristic structural and functional changes seen in detoxified alcoholics. In this chapter, we discuss some of the conceptual and methodological problems associated with what has become known as the premature-aging hypothesis and review a series of recent studies that have used neuropsychological, computerized-tomography, and evoked-potential techniques to test its validity. We conclude that there is very little compelling empirical support for this intriguing hypothesis and suggest that the neurobehavioral changes seen in alcoholics are merely the reflection of a diffusely distributed pattern of brain damage.

Limbic seizures produced by pilocarpine in rats: Behavioural, electroencephalographic and neuropathological study

Behavioural, electroencephalographic and neuropathological responses to increasing doses of pilocarpine (100–400 mg/kg) administered intraperitoneally to rats were studied. At the dose of 400 mg/kg pilocarpine produced a sequence of behavioural alterations including staring spells, olfactory and gustatory automatisms and motor limbic seizures that developed over 1–2 h and built up progressively into limbic status epilepticus. Smaller doses showed different threshold for these behavioural phenomena but a similar time course of development. The earliest electrographic alterations occurred in the hippocampus and then epileptiform activity propagated to amygdala and cortex. Subsequently electrographic seizures appeared in both limbic and cortical leads. The ictal periods recurred each 5–15 min and were followed by variable periods of depression of the electrographic activity. The sequence of electrographic changes correlated well with the development of behavioural phenomena. Histological examination of frontal forebrain sections revealed disseminated, apparently seizure-mediated pattern of brain damage. Neuropathological alterations were observed in the olfactory cortex, amygdaloid complex, thalamus, neocortex, hippocampal formation and substantia nigra. Pretreatment of animals with scopolamine (20 mg/kg) and diazepam (10 mg/kg) prevented the development of convulsive activity and brain damage. These results show that systemic pilocarpine in rats selectively elaborates epileptiform activity in the limbic structures accompanied by motor limbic seizures, limbic status epilepticus and widespread brain damage. It is suggested that a causative relationship between excessive stimulation of cholinergic receptors in the brain and epileptic brain damage may exist.

Intrahippocampal bethanechol in rats: Behavioural, electroencephalographic and neuropathological correlates

Unilateral microinjections of bethanechol chloride into the CA3 subfield of the dorsal hippocampus in unrestrained rats produced a seizure-related type behavioural and disseminated brain damage syndrome. Injection of bethanechol in the dose of 50 μg resulted in locomotor activation, mouth movements, teeth chattering, chewing, wet dog shakes and mild limbic seizures. Shortly after intrahippocampal injection the electroencephalogram (EEG) showed an increase in the frequency of the theta rhythm in both hippocampi. Then EEG showed spiking activity of high frequency in the injected hippocampus, with rapid propagation to the lateral septum, amygdala, neocortex and contralateral hippocampus. The periods of spiking activity of high frequency were followed by depression in the background EEG rhythm with some interspersed spike and wave complexes of very low frequency. Histological examination of frontal forebrain sections revealed disseminated, apparently seizure-mediated pattern of brain damage. The patterning of distant damage after intrahippocampal injections of bethanechol involved the piriform cortex, entorhinal cortex, olfactory tubercle, anterior olfactory nucleus, subiculum, amygdaloid complex, temporoparietal cortex and hypothalamic nuclei. Neuropathological alterations were occasionally observed in the lateral septum and thalamus. These results seem to establish a causative relationship between excessive stimulation of cholinergic muscarinic receptors in the hippocampal formation and epileptic brain damage.

Intraamygdaloid morphine produces seizures and brain damage in rats

Behavioral and neuropathological responses to increasing doses of morphine hydrochloride (10–75 μg) administered into the rat amygdala were studied. Unilateral microinjections of morphine in doses of 40 and 75 μg produced a sequence of behavioral alterations including staring spells, gustatory automatisms, wet dog shakes, motor limbic seizures and limbic status epilepticus. Lower doses of morphine (10 and 20 μg) showed different threshold for these behavioral phenomena but a similar time course of development. Histological examination of frontal forebrain sections revealed widespread, apparently seizure-mediated pattern of brain damage. Neuropathological alterations were observed in the olfactory cortex, thalamus, neocortex, hippocampal formation and amygdaloid complex. Pretreatment of animals with diazepam (10 mg/kg i.p.) prevented the development of sustained limbic seizures and brain damage caused by morphine, while pretreatment with naloxone hydrochloride (2–20 mg/kg i.p.) failed to affect morphine-induced convulsant activity and brain damage. These results may suggest that morphine elaborates sustained limbic seizures and widespread brain damage by mechanism underlying the antagonism of inhibitory amino acid neurotransmission and opioid receptors do not seem to be involved.

Morphological damage to the premature fetal rat brain after acute carbon monoxide exposure

On gestational day 15 pregnant female rats were exposed 3 h to carbon monoxide (CO) in a dynamic flow chamber. The concentration of CO was approximately 0.1% in filtered air and maternal carboxyhemoglobin attained 50% during the exposure. Rat fetuses were taken by cesarean section on gestational day 16, 24 h after the exposure, for histological evaluation of the central nervous system. The ventral germinal matrix overlying the developing caudate nucleus was the region most consistently and severely damaged by CO exposure. Hemorrhagic infarcts with necrosis in this germinal matrix and cavities with cellular debris were characteristic observations in the developing caudate of CO-exposed fetuses. In contrast, the dorsal germinal matrix of the neopallium was not damaged by CO exposure. The ventral germinal matrix was less well vascularized and more developed than the dorsal region at this gestational age. The findings suggest that the combination of limited vascularity and high proliferative activity, characteristic of the germinal matrix of the developing caudate at this stage, can explain the selective vulnerability to hypoxic damage. The pattern of damage seen in our rats was similar to the deep periventricular pattern of brain damage observed in premature human newborns after acute hypoxic episodes.

The role of epileptic activity in hippocampal and ‘remote’ cerebral lesions induced by kainic acid

Kainic acid (KA) was injected systemically, intracerebroventricularly (i.c.v.) and focally in the amygdala and other deep brain structures in the rat. EEG and behavioral changes were studied in relation to the neuropathology which developed subsequently. Following intra-amygdaloid KA injection, diazepam blocked the epileptic events induced by the toxin, and abolished the neuronal loss usually seen in the lateral septum, claustrum, and contralateral cortex and hippocampus. The lesions in medial thalamic structures and ipsilateral hippocampus were also reduced by diazepam. Prior transection of the perforant path ipsilateral to the KA injection also decreased the severity of the electrographic and motor effects of the toxin and similarly reduced the extent of distant (‘remote’) pathological brain damage. Neither diazepam nor perforant path transection reduced the damage at the site of KA injection. Kainic acid (0.4–2 μg) injected into the bed nucleus of the stria terminalis (BST) or the medial septum produced seizures with a longer latency and little brain damage outside the injection site. In contrast, intrastriatal KA injections were followed by ipsilateral hippocampal lesions. i.c.v. Injection of KA (0.4–1.6 μg) produced a complex syndrome which included bilateral exophthalmos, mydriasis, foaming, tremor of the vibrissae, and paw and body tremor. The pattern of brain damage resembled that seen following intra-amygdaloid administration of the toxin. In addition, however, there was a bilateral necrosis of the pyriform and prepyriform cortices up to the rhinal fissure. Systemic administration of diazepam (i.p.) reduced the extent of the damage and in particular completely prevented the cortical damage. Systemic administration of KA (9–15 mg/kg i.p.) readily produced motor and EEG seizures similar to those seen after intra-amygdaloid injection of the toxin. The pattern of brain damage was however more symmetrical than that which followed focal i.c.v. injection of the toxin and included necrosis of the pyriform cortex. It is concluded that spread of seizure activity from the injection site plays a crucial role in the induction of ‘remote’ brain damage after focal intracerebral injections.

Acute dendrotoxic changes in the hippocampus of kainate treated rats

Kainic acid (KA), a potent neuroexcitatory and neurotoxic analog of glutamate (Glu), induces a widespread pattern of brain damage when administered subcutaneously to adult rats. The hippocampus is among the brain regions most consistently and severely damaged. Here we describe acute swelling of certain spines and branchlets of dendrites as the first detectable sign of KA neurotoxic changes in the hippocampus. These swellings conform to a laminar pattern suggesting selective toxic interaction of KA at specific levels of the dendritic trees of hippocampal pyramidal and dentate granule neurons. The frequency and severity of involvement of each type of hippocampal neuron at each level of its dendritic tree was roughly estimated and neuronal types were ranked from the most to least extensively involved (CA3 > CA4 > CA1 > CA2 > dentate granules). The same rank order has been described for the vulnerability of these neurons to acute destruction following intraventricular KA administration. Because the pattern of dendritic dilatations observed corresponds well with the pattern of termination of putative glutamergic inputs to the hippocampus, we interpret the findings as being consistent with the hypothesis that the toxic effects of KA are mediated through glutamergic excitatory receptors. We propose that the sensitivity of a given neuron to the neurodestructive action of KA may be determined by the percentage of its dendritic surface occupied by Glu receptors. We suspect that most, if not all, hippocampal neurons receive some glutamergic input and, therefore, are sensitive to KA. That CA3 pyramids are substantially more sensitive than dentate granules may signify that the former receive many more Glu terminals than the latter, an assumption quite consistent with our observation that focal dendritic swellings were both more densely and more widely distributed over the dendritic surfaces of the former than the latter.

Three patterns of brain damage of the WAIS.

Compared four groups of matched Ss (40 each) in order to examine different subtest patterns of brain damage on the WAIS, using F-tests and age mean profiles. The groups were: Normals, diffuse cortical degeneration, right and left hemisphere damage. The results indicated three patterns: (1) a normal pattern; (2) a diffuse degenerative and right hemisphere pattern; and (3) a left hemisphere pattern. The diffuse degenerative results were not significantly different from the right hemisphere results. The left hemisphere pattern had no large verbal vs. performance differences. These patterns appear to be produced by the interaction of three brain damage effects: (1) a general effect; (2) a right hemisphere effect; and (3) a left hemisphere effect. Verbal tests are both "hold" and left hemisphere tests, while three Performance Tests are "don't hold" and right hemisphere tests. The WAIS requires other specific tests of brain damage for an adequate assessment of brain damage.

Patterns of Brain Damage in Infants and Children With Congenital Heart Disease

Detailed histologic analysis of the brain in 500 patients with congenital heart defects revealed a relatively common occurrence (above 17%) of thromboembolic infarctions. They occurred four to five times more often in surgical than in nonsurgical cases, with 18 in direct association with catheterization and 21 following catheterization and surgical procedures. Careful search of meningeal arteries around infarcted areas is essential for recognizing the thromboemboli. Anoxic cortical necroses, diffuse or segmental, were four times higher in the surgical group, depending on gradual or rapid reduction of blood flow during and after cardiac surgery. Except for the early infancy group, venous thromboses causing infarctions were uncommon. Cardiac catheterization within the neonatal period proved hazardous in 21 cases in infants with severe anomalies. Continued febrile episodes following catheterization or surgery might suggest an acquired or preexisting encephalitis for which viral studies are indicated.