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Biomedical subjects

W L Maxwell

Publications and source records attributed to W L Maxwell.

At least 37 records · Page 2Linked to original sources
PubMed1995

The nature, distribution and causes of traumatic brain injury.

The identification and interpretation of brain damage resulting from a non-missile head injury is often not easy with the result that the most obvious structural damage identified postmortem may not be the most important in trying to establish clinicopathological correlations. For example patients with a fracture of the skull, quite severe cerebral contusions or a large intracranial haematoma that is successfully treated can make an uneventful and complete recovery if no other types of brain damage are present. However, not infrequently more subtle forms of pathology are present and ones that can only be identified microscopically. A systematic and pragmatic approach through the autopsy is therefore required and one that recognises the need for tissue to be retained in ways that are appropriate for cellular and molecular studies.

Apolipoproteins E↗
PubMed1994

Diffuse astrocytic swelling and increased second messenger activity following acute Haemophilus influenzae meningitis--evidence from a rat model.

Despite numerous epidemiological analyses of bacterial meningitis there is very little pathological data concerning the acute glial and neuronal responses to the disease. We have developed a safe, easily used rat model for Haemophilus influenzae type b meningitis. We measured cerebral blood flow, glucose utilisation and second messenger activity in this model, and carried out parallel light and ultrastructural analysis of glial and neuronal responses. Only protein kinase C activity was changed from control values. We obtained evidence for massive astrocytic swelling and neuronal degeneration. We posit that cytotoxic mechanisms may contribute to the pathology of meningitis.

Adenylyl Cyclases↗
PubMed1994

Massive astrocytic swelling in response to extracellular glutamate--a possible mechanism for post-traumatic brain swelling?

Little attention has been paid to the responses of astrocytes in the brain to the application of neurotoxic excitatory transmitters such as glutamate. We have developed a simple model to study the responses of cells within the cerebral cortex to neurotoxic levels of glutamate. After short periods of perfusion with glutamate, perivascular and interstitial astrocytes swell and become electron lucent. The astrocyte swelling extends, with increasing periods of perfusion, up to 400 um into the adjacent, intact neuropil. After 90 minutes of glutamate perfusion, intermediate filament bundles and glycogen granules occur within the astrocyte cytoplasm. We obtained no evidence for compromised blood flow. We suggest that astrocyte swelling serves to limit the diffusion of glutamate from the site of the lesion.

Animals↗
PubMed1994

Focal microvascular occlusion after acute subdural haematoma in the rat: a mechanism for ischaemic damage and brain swelling?

Using a rat model of subdural haematoma (SDH) which is associated with ischaemic damage in the ipsilateral hemisphere, we have studied the microcirculation and the time course of development of ischaemia beneath the subdural haematoma. The latter was investigated by measuring cerebral blood flow (CBF) using the hydrogen clearance technique, the former by electron microscopy (EM) and carbon black angiography. CBF fell below 5 ml/100g/min within five minutes of SDH and remained low (< or = 7 ml/100g/min) for over two hours. Contralateral CBF fell to 54% of control but normalized by 1 hour. Carbon black angiography showed absent perfusion beneath the SDH. EM demonstrated: 1) normal cortical vessel traversing the haematoma; 2) occlusion of cortical vessels under SDH by clotted red cells and platelets; 3) massively enlarged perivascular spaces due to swelling of astrocytes. No vasospasm was seen. The "ischaemic core" may develop where microvascular occlusion occurs, and this microcirculatory disturbance initiates ischaemic cell damage with release of glutamate, which spreads outward from the core. This causes further damage of neurons and swelling of astrocytes, resulting in severe ischaemic necrosis, and progressive brain edema. The cause of microvessel occlusion remains unknown.

Animals↗
PubMed1994

A qualitative and quantitative analysis of the response of the retinal ganglion cell soma after stretch injury to the adult guinea-pig optic nerve.

The development of a model for focal axonal injury in the optic nerve of the adult guinea-pig has allowed a qualitative and quantitative analysis of the response of the retinal ganglion cell soma to this type of injury. Large and medium sized retinal ganglion cells show classic 'central chromatolysis' in about 30% of ganglion cells between three and seven days after injury, a high proportion of which undergo degeneration between seven and 14 days. Small ganglion cells and small neurons do not demonstrate any morphological response to stretch injury of the optic nerve. However, a small number of larger ganglion cells demonstrate enlargement of the cell soma and nucleolus together with reconstitution of the rough endoplasmic reticulum between seven and 14 days after stretch injury. We suggest that these cells are either recovering from or regenerating after a non-disruptive lesion to their axons. We suggest that some of these morphological changes parallel documented regenerative responses in peripheral/extrinsic neurons after injury to their axons. We conclude that the time course of the 'axon reaction' after stretch injury to axons is longer than that obtained after crush or transection. We provide good morphological evidence that the level of injury after application of non-disruptive mechanical strain to axons is less severe than in the former two models of axonal injury and that a proportion of damaged neurons do not die but rather demonstrate either/or recovery or a regenerative response.

Animals↗
PubMed1993

Traumatic damage to the nodal axolemma: an early, secondary injury.

Electronmicroscopical investigations were made in a model of optic nerve damage in guinea-pigs on the development of acute axonal damage on an ultrastructural basis. It was expected to obtain thereby further information on mechanisms underlying axonal damage in traumatic brain injury. For that purpose an injury apparatus was employed to deliver defined elongation and/or tensile strains to the optic nerve. Transmission electronmicrographs were examined of longitudinal and transverse nerve sections throughout its entire length. The most severe abnormalities were identified in the prechiasmatic portion of the nerve. Among others, elongations of the nodes of Ranvier were encountered, swollen axons with accumulation of organelles, and even disrupted axons having a morphology similar to retraction balls. In all instances, abnormal axons were found together with axons having a normal structural appearance. Nodes of Ranvier demonstrated outward dilatations of the nodal axolemma and of the adjacent axoplasm, which are named as nodal blebs. Nodal blebs occurred already 15 min after injury, and were fully developed at 6 or 24 hrs. The blebs had disappeared again after 5-7 days. The axoplasm in the blebs demonstrated considerable disorganization of cytoskeletal elements with an array of amorphous material appearing as granular degeneration. Taken together, the present experimental model is a useful approach to analyse axonal damage at the ultrastructural level as it may occur in white matter of the central nervous system.

Animals↗
PubMed1993

Ultrastructural evidence of axonal shearing as a result of lateral acceleration of the head in non-human primates.

The concept of shearing of axons at the time of non-impact injury to the head was first suggested in the middle of this century. However, no experimental model of diffuse axonal injury (DAI) has provided morphological confirmation of this concept. Evidence from experiments on invertebrate axons suggests that membrane resealing after axonal transection occurs between 5 and 30 min after injury. Thus, ultrastructural evidence in support of axonal shearing will probably only be obtained by examination of very short-term survival animal models. We have examined serial thin sections from the corpus callosum of non-human primates exposed to lateral acceleration of the head under conditions which induce DAI. Tearing or shearing of axons was obtained 20 and 35 min after injury, but not at 60 min. Axonal fragmentation occurred more frequently at the node/paranode but also in the internodal regions of axons. Fragmentation occurred most frequently in small axons. Axonal shearing was associated with dissolution of the cytoskeleton and the occurrence of individual, morphologically abnormal membranous organelles. There was no aggregation of membranous organelles at 20 and 35 min but small groups did occur in some axons at 60 minutes. We suggest that two different mechanisms of injury may be occurring in non-impact injury to the head. The first is shearing of axons and sealing of fragmented axonal membranes within 60 min. A second mechanism occurs in other fibres where perturbation of the axon results in axonal swelling and disconnection at a minimum of 2 h after injury.

Acceleration↗
PubMed1992

The cerebrovascular response to experimental lateral head acceleration.

A number of microvascular changes, such as the development of astrocyte lucency, increased endothelial pit/vesicle activity, development of crater like lesions, and endothelial microvilli have been reported after injury to the brain. Lateral head acceleration in the non-human primate, however, still provides the best experimental model for human diffuse axonal injury. No attempt has yet been made to document the spatial extent or time course of the microvascular response to acceleration injury to the head. We have examined the brains of baboons 1, 4, 6, and 12 h and 7 days after acceleration injury to the head to analyse the microvascular response. In the experimental animals there was a short-term rise in intracranial pressure followed by a long-term resolution, and a reduction in both mean arterial blood pressure and cerebral perfusion pressure which, however, never dropped below 75% of baseline for more than 5 min after injury in any animal. We found evidence for extravasation of blood in a small number of blood vessels in all parts of the brain. Interendothelial tight junctions are not disrupted. Pit/vesicle activity rises in the 1st h in the occipital cortex, but not until 4 h in the frontal cortex, and remains elevated for at least 7 days. There is little change in the thalamus. Development of microvilli is most rapid in the frontal cortex with peak values at 1 h, but slower in the thalamus and occipital cortex where peak values are only obtained at 6 h. Highest numbers of microvilli occur in parasagittal regions of the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Acceleration↗
PubMed1992

Changes in the choroid plexus, responses by intrinsic epiplexus cells and recruitment from monocytes after experimental head acceleration injury in the non-human primate.

We have examined, by scanning and transmission electron microscopy, morphological changes in the choroid plexus of the lateral ventricles of the non-human primate brain after lateral head acceleration. We demonstrate passage of plasma and blood cells either through tears in blood vessels and the choroidal epithelium, or through the cells of the choroidal epithelium, 20 min after injury, together with morphological changes in that epithelium. At 3 and 4 h small cells with a reniform nucleus accumulate in the connective tissue core of the choroid plexus. We suggest that these are monocytes. At 6 and 12 h cells can be seen in enlarged intercellular spaces within the choroidal epithelium. These cells possess surface ruffles and we suggest that they are monocytes differentiating into macrophages and epiplexus cells. Further evidence for transepithelial migration of monocytes/macrophages is obtained at 7 days. However, at 28 days all blood has been removed from the surface of the choroid plexus and epiplexus cells possess an appearance typical of that in uninjured animals. The possible sources of epiplexus cells are discussed with reference to studies of responses after brain insult and of development. We have obtained no evidence in support of emperipolesis by monocytes through the choroidal epithelium. We suggest that monocytes/macrophages migrate, via an intercellular route, to differentiate into epiplexus cells, thus providing additional numbers of epiplexus cells after head injury.

Acceleration↗
PubMed1991

Focal axonal injury: the early axonal response to stretch.

The development of a model for axonal injury in the optic nerve of the guinea pig has allowed analysis of early morphological changes within damaged axons. We provide evidence that the initial site of damage after stretch is the nodes of Ranvier, some of which develop 'nodal blebs'. The development of nodel blebs is correlated with the loss of subaxolemmal density, disruption of the neurofilament cytoskeleton and aggregation of membranous profiles of smooth endoplasmic reticulum. Nodal blebs are numerous 15 min after injury but less so at later survivals. The glial-axonal junction is intact at early survivals in damaged nodes. Marked accumulation of membranous organelles occurs in the paranodal and internodal regions adjacent to damaged nodes between two and six hours and is correlated with disruption of the myelin sheath. Axotomy and the formation of degeneration bulbs occurs between 24 and 72 h. The area of axonal injury is invaded by phagocytic cells by 72 h and large numbers of myelin figures occur within the neuropil until 14 days. The results are compared with those of other studies of diffuse axonal injury and other neuropathies. The time course of axonal changes is more rapid than during Wallerian degeneration. Our data from longer surviving animals is exactly comparable with published data. We are confident that the principal site of axonal injury is the node of Ranvier. We suggest that damage at the node results in disruption of axonal transport, which in turn leads to a cascade of events, culminating in axotomy between 24 and 72 h after the initial insult.

Animals↗
PubMed1991

The microvascular response to stretch injury in the adult guinea pig visual system.

In a variety of brain injury models, both reactive axonal change and microvascular abnormalities occur. Development of a stretch injury model in the guinea pig optic nerve has allowed for the characterization of the early axonal response to injury. In this same model, we have now attempted to characterize those morphologic changes occurring in the visual system microvasculature after injury. Thirty adult guinea pigs were subjected to axonal stretch injury and killed at posttraumatic survival periods ranging from 10 minutes to 14 days. Twenty animals were examined by scanning electron microscopy (SEM) for the detection of posttraumatic changes in the surface morphology of the microvasculature, and 10 animals were processed for transmission electron microscopy (TEM) analysis. Through this approach, increased pit vesicle activity and formation of endothelial microvilli were recognized within 10 minutes of injury. Pit vesicle activity returned to control levels by 2 hours. The formation of endothelial microvilli was widespread, affecting the microvessels in both the stretched and unstretched optic nerves and in the chiasm. The greatest response developed most slowly in the stretched nerve, and it was faster but less marked in the unstretched nerve and chiasm. Microvilli were more numerous in larger vessels. Related astrocytic swelling/lucency was not apparent until 6 hours after injury. The astrocyte response was less marked than that documented after brain injury. The results of this investigation demonstrate a widespread microvascular response to stretch injury of the guinea pig optic nerve. Comparison with the documented responses to traumatic brain injury indicates different rates of response to different types of insult.

Animals↗
PubMed1991

Glial swelling following human cerebral contusion: an ultrastructural study.

The ultrastructural features of cerebral contusion seen three hours to 11 days after head injury were studied in 18 patients undergoing surgery. Massive astrocytic swelling ("cytotoxic" oedema) was seen three hours to three days after injury, maximal in perivascular foot processes, and compressing some of the underlying capillaries. The tight junctions were not disrupted. Neuronal damage was most marked three to 11 days after injury. The pathophysiological mechanisms leading to oedema formation and neuronal degeneration are discussed.

Adult↗
PubMed1991

Localisation of calcium ions and calcium-ATPase activity within myelinated nerve fibres of the adult guinea-pig optic nerve.

There is no published description of the distribution of free Ca2+, nor of the distribution of Ca(2+)-ATPase activity associated with the maintenance of low axoplasmic Ca2+ concentrations, in normal central myelinated nerve fibres. We have used the oxalate-pyroantimonate technique to localise free Ca2+, together with the lead-citrate technique to localise Ca(2+)-ATPase activity within myelinated fibres from the adult guinea-pig optic nerve. Pyroantimonate precipitate occurred within the axoplasm at nodes of Ranvier and the internode, at areas of myelin disruption, within Schmidt-Lanterman incisures (SLI) and glial paranodal loops. But precipitate was absent from the axoplasm beneath SLI and at the paranode. Ca(2+)-ATPase activity was localised in axonal smooth endoplasmic reticulum (SER), the outer membrane of mitochondria, the nodal axolemma, the glial membranes of the paranodal loops, the SLI and the external aspect of the myelin sheath. We have demonstrated large domains within the axons of CNS fibres where calcium is present or absent. Moreover, we have shown that, where calcium is absent, there is localisation of Ca(2+)-ATPase activity, which would serve to remove calcium from the adjacent axoplasm. Our results are compared with information obtained from PNS fibres and some differences of distribution discussed.

Animals↗
PubMed1990

Glycogen accumulation in axons after stretch injury.

Thin-section cytochemistry has been used to demonstrate the formation of glycogen deposits within axons after stretch injury to the optic nerve of adult guinea pigs in a model of focal axonal injury. Glycogen deposits occurred within 17% of structurally normal but, we suggest, damaged fibres within the stretched optic nerve. Adjacent fibres did not stain for glycogen. Small numbers of beta glycogen particles were present 15 min after injury within damaged axons and increasing numbers of particles occurred until 72 h. Degeneration bulbs formed by 72 h, but beta glycogen particles were sparse within these. By 7-14 days after injury there was a marked reduction in the numbers of glycogen particles within axons. Alpha rosettes of glycogen were infrequent within damaged axons. Deposition of glycogen particles within astrocytes after nerve injury was confirmed. Alpha rosettes of glycogen occurred within astrocytes by 6 h and remained until 14 days after injury. Possible mechanisms for the development of glycogen deposits within damaged axons are discussed in relation to a hypothesized influx of Ca2+ at the time of injury into damaged axons. We suggest that glycogen deposition within reactive axons reflects Ca2+ mediated alteration of glycogen synthase activity and compromized axonal transport.

Animals↗