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Biomedical subjects

T A Gennarelli

Publications and source records attributed to T A Gennarelli.

At least 19 recordsLinked to original sources
PubMed2001

Extensive subdural mass.

An unusual case of a 62-year-old man with focal seizures, tinnitus, and progressive left hemiparesis due to an extensive subdural plasma cell granuloma is presented. Five-year clinical and radiologic follow-up demonstrating the chronic yet progressive nature of this granuloma is presented. This is the first report of focal calcification seen in an intracranial plasma cell granuloma. The imaging, neuropathologic, and clinical characteristics of this rare lesion are reviewed.

Brain Diseases↗
PubMed2001

Biomechanical modeling of penetrating traumatic head injuries: a finite element approach.

Due to advances in emergency medical care and modern techniques, treatment of gunshot wounds to the brain have improved and saved many lives. These advances were largely achieved using retrospective analysis of patients with recommendations for treatment. Biomechanical quantification of intracranial deformation/stress distribution associated with the type of weapon (e.g., projectile geometry) will advance clinical understanding of the mechanics of penetrating trauma. The present study was designed to delineate the biomechanical behavior of the human head under penetrating impact of two different projectile geometry using a nonlinear, three-dimensional finite element model. The human head model included the skull and brain. The qualitative comparison of the model output with each type of projectile during various time steps indicated that the deformation/stress progressed as the projectile penetrated the tissues. There is also a distinct difference in the patterns of displacement for each type of projectile. This observation matches our previous study using a physical gelatin model of delineate the penetrating wound profiles for different projectile types. The present study is a first step in the study of biomechanical modeling of penetrating traumatic brain injuries.

Biomechanical Phenomena↗
PubMed2001

Sphenoid sinus mucocele: a rare complication of transsphenoidal hypophysectomy.

Only seven cases of a sphenoid mucocele occurring after transsphenoidal hypophysectomy have been previously reported in the world literature. In this article, we report a new case, which occurred in a 67-year-old man. The sphenoid sinus mucocele developed 12 years following transsphenoidal hypophysectomy and adjunctive radiotherapy. The patient was successfully managed with incision and drainage. Although transsphenoidal hypophysectomy is a common operation, this particular complication appears to be rare or at least under-reported. Sphenoid sinus mucocele deserves consideration in the differential diagnosis of a sphenoidal parasellar mass in a patient who has undergone an earlier transsphenoidal hypophysectomy.

Aged↗
PubMed2000

Airbag effectiveness on brain trauma in frontal crashes.

The purpose of this study was to evaluate the effectiveness of frontal restraint systems in reducing the potential for head injuries, specifically brain injuries and skull fractures. The US DOT NASS database files from 1991-1998 were evaluated for drivers and right front seat occupants in frontal crashes. Of the total driver and right front seat occupants in this data set, 3.83% sustained a brain injury without skull fracture, 0.05% sustained a skull fracture without a brain injury, and 0.16% sustained both brain injury and skull fracture. The incidence of head injury was lowest among occupants who were restrained by belt alone (2.76%) and by both airbag and belt systems (3.51%). The unrestrained population had a 10.39% incidence of at least one type of head injury. In general, for maximum AIS > or = 2 head injuries, airbag effectiveness was greatest between 16-45 kph crash delta V. For the more severe maximum AIS > or = 3 head injuries, the airbag restraint had its greatest effect up to 35 kph. It can be concluded that brain injury in frontal crashes is substantially reduced with the presence of a restraint system and the use of both airbag and belt restraint offers the greatest protection across all delta V categories. Restraint system effectiveness for the non-head-injured occupant is variable but, generally, the belted occupant sustained the lowest percentage of injuries. Skull fractures in frontal impact were relatively rare and the incidence appeared to be unaffected by the presence of a restraint system.

Accidents, Traffic↗
PubMed2000

Patterns of abdominal injuries in frontal and side impacts.

Public awareness for safety and vehicle improvements has contributed to significant reduction in injuries secondary to motor vehicle crashes. The spectrum of trauma has shifted from one region of the body to another with varying consequences. For example, airbags have minimized head and neck injuries for adults while emphasizing the lower regions of the human body. Studies have concentrated on the changing patterns of these injuries in frontal impacts. However, there is almost a paucity of data with regard to the characterization of abdominal injuries. Consequently, this study was conducted to determine the patterns of abdominal injuries in frontal and side impacts with an emphasis on more recent crashes. In particular, the frequency and severity of trauma were investigated with a focus on the various abdominal organs (e.g., spleen and liver). Results indicate that side crashes contribute to a large percentage of injuries to the abdomen. The liver and spleen organs are most vulnerable; therefore, it may be beneficial to apply concerted efforts to focus on injury biomechanics research and prioritization activities in these areas of the abdomen. These data may be of benefit to develop anthropomorphic dummies with improved biofidelity.

Abdominal Injuries↗
PubMed1999

Experimental investigation of cerebral contusion: histopathological and immunohistochemical evaluation of dynamic cortical deformation.

We used a new approach, termed dynamic cortical deformation (DCD), to study the neuronal, vascular, and glial responses that occur in focal cerebral contusions. DCD produces experimental contusion by rapidly deforming the cerebral cortex with a transient, nonablative vacuum pulse of short duration (25 milliseconds) to mimic the circumstances of traumatic injury. A neuropathological evaluation was performed on brain tissue from adult rats sacrificed 3 days following induction of either moderate (4 psi, n = 6) or high (8 psi, n = 6) severity DCD. In all animals, DCD produced focal hemorrhagic lesions at the vacuum site without overt damage to other regions. Examination of histological sections showed localized gross tissue and neuronal loss in the cortex at the injury site, with the volume of cell loss dependent upon the mechanical loading (p < 0.001). Axonal pathology shown with neurofilament immunostaining (SMI-31 and SMI-32) was observed in the subcortical white matter inferior to the injury site and in the ipsilateral internal capsule. No axonal injury was observed in the contralateral hemisphere or in any remote regions. Glial fibrillary acidic protein (GFAP) immunostaining revealed widespread reactive astrocytosis surrounding the necrotic region in the ipsilateral cortex. This analysis confirms that rapid mechanical deformation of the cortex induces focal contusions in the absence of primary damage to remote areas 3 days following injury. Although it is suggested that massive release of neurotoxic substances from a contusion may cause damage throughout the brain, these data emphasize the importance of combined injury mechanisms, e.g. mechanical distortion and excitatory amino acid mediated damage, that underlie the complex pathology patterns observed in traumatic brain injury.

Animals↗
PubMed1998

Suprasellar osteolipoma: case report.

BACKGROUND: Osteolipomas are distinguished from other intracranial lipomas by their arrangement of central adipose and peripheral osseous tissues and by characteristically arising in the suprasellar/interpeduncular region. METHODS: We report computed tomography (CT), magnetic resonance imaging (MRI), and pathology findings from this 34-year-old man who underwent surgical removal of this benign lesion. RESULTS: This case displays the distinctive histopathology that has been reported in 13 of 31 (42%) lipomas in this region. In contrast, ossification of lipomas at other intracranial sites is relatively rare. CONCLUSIONS: Ossification should be expected in many suprasellar/interpeduncular lipomas, and osteolipoma should be included in the radiologic differential diagnosis of fat-intensity masses with calcification in this region.

Adult↗
PubMed1998

Magnetic resonance spectroscopy of diffuse brain trauma in the pig.

The acute metabolic events linked to the evolution of selective axonal pathology in the white matter following diffuse brain injury have not previously been evaluated due to the paucity of relevant experimental models. Here, we utilized a new model of inertial brain injury in the pig that selectively damages axons in the white matter, and applied proton and phosphorous magnetic resonance spectroscopy (MRS) to noninvasively monitor the temporal course of metabolic changes following trauma. Evaluating four pigs with MRS prior to injury, within 1 h and 3 and 7 days postinjury, we found that widespread axonal injury was produced in the absence of changes in pH, PCr/Pi, or the concentrations of ATP, and lactate. However, we did observe an acute 60% loss of intracellular Mg2+ levels, which gradually resolved by 7 days postinjury. In addition, we found that the levels of the neuron marker, N-acetylaspartate (NAA), acutely dropped 20% and remained persistently decreased for at least 7 days postinjury. Moreover, the changes in Mg2+ and NAA were found with MRS in the absence of abnormalities with conventional magnetic resonance imaging (MRI). These results show that (1) profound alterations in intracellular metabolism occur acutely following diffuse axonal pathology in the white matter, but in the absence of indicators of ischemia, and (2) axonal pathology may be evaluated with high sensitivity utilizing noninvasive MRS techniques.

Adenosine Triphosphate↗
PubMed1997

Characterization of diffuse axonal pathology and selective hippocampal damage following inertial brain trauma in the pig.

Dynamic deformation applied to white matter tracts is a common feature of human brain trauma, and may result in diffuse axonal injury (DAI). To produce DAI in an experimental model, we have utilized nonimpact inertial loading to induce brain trauma in miniature swine. This species was chosen due to its large gyrencephalic brain with substantial white matter domains. Twenty anesthetized (2% isoflurane) miniature swine were subjected to pure impulsive centroidal rotation 110 degrees in the coronal plane in 4 to 6 ms; peak accelerations ranged from 0.6 to 1.7 x 10(5) rad/s2. Seven days following injury, the brains were fixed (4% paraformaldehyde). Histopathologic examination was performed on 40 microns sections stained with cresyl violet (Nissl), antibodies targeting neurofilament (axonal damage), GFAP (astrocytes), and pig IgG (protein extravasation). Widespread multifocal axonal injury was observed in combination with gliosis throughout the brain, most commonly in the root of gyri and at the interface of the gray and white matter. Very little vascular disruption was noted in regions of axonal injury. Neuronal damage was primarily found in the CA1 and CA3 subfields of the hippocampus. These results suggest that this model is clinically relevant and useful for evaluating mechanisms of inertial brain trauma.

Animals↗
PubMed1996

Is beta-APP a marker of axonal damage in short-surviving head injury?

beta-Amyloid precursor protein (beta-APP), a normal constituent of neurons which is conveyed by fast axonal transport, has been found to be a useful marker for axonal damage in cases of fatal head injury. Immunocytochemistry for beta-APP is a more sensitive technique for identifying axonal injury than conventional silver impregnation. This study was designed to determine how quickly evidence of axonal damage and bulb formation appears. Using this method a variety of brain areas were studied from 55 patients who died within 24 h of a head injury. Immunocytochemical evidence of axonal injury was first detected after 2 h survival, axonal bulbs were first identified after 3 h survival, and the amount of axonal damage and axonal bulb formation increased the longer the survival time.

Adolescent↗
PubMed1996

Transfection of human lactotroph adenoma cells with an adenovirus vector expressing tyrosine hydroxylase decreases prolactin release.

Pituitary adenomas are common intracranial neoplasms, for which surgery and radiation are usually not curative. In attempting to develop gene therapy as a better approach to treating pituitary adenomas, we chose lactotroph adenomas as a model. The rationale for the use of this model is based on the observation that dopamine agonists decrease prolactin secretion by lactotroph adenomas, and also decrease their size. We transfected primary cultures of human lactotroph adenoma cells with an adenovirus vector containing a cDNA which encodes a human tyrosine hydroxylase, the rate-limiting enzyme in the biosynthesis of dopamine. Transfection induced expression of tyrosine hydroxylase and increased production of dopamine, resulting in the predicted biologic effect of decreased prolactin secretion. These results demonstrate the potential for gene therapy of lactotroph adenomas and perhaps other pituitary adenomas, which are less amenable to pharmacologic treatment than lactotroph adenomas.

Adenoma↗
PubMed1996

Decreased follistatin gene expression in gonadotroph adenomas.

What growth factors are involved in the pathogenesis of gonadotroph adenomas is not yet known. Activin is one possible candidate because it stimulates growth and differentiation in many cells, including the gonadotroph cell, and it stimulates FSH secretion, characteristic of gonadotroph adenomas. As activin beta B-subunit is expressed in gonadotroph adenomas, we sought to determine whether activin receptor II and follistatin are also expressed. Total ribonucleic acid (RNA) was extracted from 10 gonadotroph adenomas that did not express pit-1 and was reverse transcribed. The resulting complementary DNAs for human activin receptor II and follistatin were amplified by PCR. All 10 adenomas expressed activin receptor II messenger RNA (mRNA), as did nonadenomatous pituitary tissue. Only 2 of the 10 gonadotroph adenomas expressed detectable follistatin mRNA, although all 4 nonadenomatous pituitaries did. Quantitation of follistatin mRNA by competitive reverse transcription-PCR showed that none of the 10 gonadotroph adenomas expressed as much follistatin mRNA as did the 4 nonadenomatous pituitaries, and 8 of the 10 expressed less than 10% as much. Immunospecific staining showed follistatin in the cytoplasm of the gonadotroph cells of all 5 nonadenomatous pituitaries studied, but only faintly in 1 gonadotroph adenoma and not at all in the other 9. These results suggest that pit-1-negative gonadotroph adenomas express less follistatin mRNA and follistatin peptide than do nonadenomatous gonadotroph cells. A consequence could be less binding, and thereby enhanced effectiveness, of activin, contributing to adenoma growth.

Activin Receptors↗
PubMed1996

Neuropathological sequelae of traumatic brain injury: relationship to neurochemical and biomechanical mechanisms.

Brain injury is the leading cause of death among individuals under the age of 45 years in the United States and Europe. Recently, the neuropathologic classification of posttraumatic brain damage has provided insight into the specific mechanisms underlying traumatically induced neuronal damage and death. Studies regarding the biomechanics of brain trauma have also provided great insight into the pathophysiologic mechanisms underlying specific patterns of posttraumatic cellular death. Based upon recent clinical evaluations and biomechanical studies, laboratory models of human brain injury have been developed that faithfully reproduce a number of important features of clinical brain trauma. Biomechanical models have been used to study both the acute sequelae of brain injury and the role of neurochemical alterations in contributing to the development of secondary or delayed cellular death and damage. This report reviews and integrates the laboratory investigations linking experimental models of brain injury to clinical diagnosis and treatment.

Animals↗
PubMed1995

Axonal injury: a universal consequence of fatal closed head injury?

beta-Amyloid precursor protein immunostaining has recently been shown to be a reliable method for detecting the damage to axons associated with fatal head injury. In an attempt to compare the efficacy of this technique with conventional histological detection of axonal damage, we have reanalysed sections from a large well-characterised series of head-injured and control patients. The results indicate that the frequency of axonal injury has been vastly underestimated using conventional silver techniques, and that axonal injury may in fact be an almost universal consequence of fatal head injury.

Adolescent↗
PubMed1995

Cytochemical evidence for redistribution of membrane pump calcium-ATPase and ecto-Ca-ATPase activity, and calcium influx in myelinated nerve fibres of the optic nerve after stretch injury.

There has been controversy for some time as to whether a posttraumatic influx of calcium ions occurs in stretch/nondisruptively injured axons within the central nervous system in both human diffuse axonal injury and a variety of models of such injury. We have used the oxalate/pyroantimonate technique to provide cytochemical evidence in support of such an ionic influx after focal axonal injury to normoxic guinea pig optic nerve axons, a model for human diffuse axonal injury. We present evidence for morphological changes within 15 min of injury where aggregates of pyroantimonate precipitate occur in nodal blebs at nodes of Ranvier, in focal swellings within axonal mitochondria, and at localized sites of separation of myelin lamellae. In parallel with these studies, we have used cytochemical techniques for localization of membrane pump Ca(2+)-ATPase and ecto-Ca-ATPase activity. There is loss of labelling for membrane pump Ca(2+)-ATPase activity on the nodal axolemma, together with loss of ecto-Ca-ATPase from the external aspect of the myelin sheath at sites of focal separation of myelin lamellae. Disruption of myelin lamellae and loss of ecto-Ca-ATPase activity becomes widespread between 1 and 4 h after injury. This is correlated with both infolding and retraction of the axolemma from the internal aspect of the myelin sheath to form periaxonal spaces which are characterized by aggregates of pyroantimonate precipitate, and the development of myelin intrusions into invaginations of the axolemma such that the regular profile of the axon is lost. There is novel labelling of membrane pump Ca(2+)-ATPase on the cytoplasmic aspect of the internodal axolemma between 1 and 4 h after injury. There is loss of an organized axonal cytoskeleton in a proportion of nerve fibres by 4-6 h after injury. We suggest that these changes demonstrate a progressive pathology linked to calcium ion influx after stretch (non-disruptive) axonal injury to optic nerve myelinated fibres. We posit that calcium influx, linked to or correlated with changes in Ca(2+)-ATPase activities, results in dissolution of the axonal cytoskeleton and axotomy between 4 and 6 h after the initial insult to axons.

Adenosine Triphosphatases↗
PubMed1995

Regional induction of c-fos and heat shock protein-72 mRNA following fluid-percussion brain injury in the rat.

To evaluate the cellular response to traumatic brain injury, the expression of mRNA for c-fos and the 72-kDa heat shock protein (hsp72) was determined using in situ hybridization following lateral fluid-percussion injury (2.2-2.4 atm) in rat brain. At 2 h after injury, induction of c-fos mRNA was observed throughout the cortex ipsilateral to the site of injury, while increased expression of hsp72 mRNA was restricted to regions of the cortex surrounding the contusion area. An increase in c-fos mRNA, but not hsp72 mRNA, was observed bilaterally in the CA3 subfield of the hippocampus and the granule cells of the dentate gyrus and in the thalamus ipsilateral to the impact site. By 6 h, increased expression of c-fos mRNA was observed only in the corpus callosum on the impact side; hsp72 mRNA persisted in the deep cortical layers and upper layers of the subcortical white matter below the site of maximal injury. By 24 h, both c-fos and hsp72 mRNA had returned to control levels in all regions of the brain. These results demonstrate that lateral fluid-percussion brain injury triggers regionally and temporally specific expression of c-fos and hsp72 mRNA, which may be suggestive of differential neurochemical alterations in neurons and glia following experimental brain injury.

Animals↗
PubMed1995

The sodium channel blocker and glutamate release inhibitor BW1003C87 and magnesium attenuate regional cerebral edema following experimental brain injury in the rat.

Excitatory amino acid (EAA) neurotransmitters may play a role in the pathophysiology of traumatic injury to the CNS. Although NMDA receptor antagonists have been reported to have therapeutic efficacy in animal models of brain injury, these compounds may have unacceptable toxicity for clinical use. One alternative approach is to inhibit the release of EAAs following traumatic injury. The present study examined the effects of administration of a novel sodium channel blocker and EAA release inhibitor, BW1003C87, or the NMDA receptor-associated ion channel blocker magnesium chloride on cerebral edema formation following experimental brain injury in the rat. Animals (n = 33) were subjected to fluid percussion brain injury of moderate severity (2.3 atm) over the left parietal cortex. Fifteen minutes after injury, the animals received a constant infusion of BW1003C87 (10 mg/kg, i.v.), magnesium chloride (300 mumol/kg, i.v.), or saline over 15 min (2.75 ml/kg/15 min). In all animals, regional tissue water content in brain was assessed at 48 h after injury, using the wet weight/dry weight technique. In saline-treated control animals, fluid percussion brain injury produced significant regional brain edema in injured left parietal cortex (p < 0.001), the cortical area adjacent to the site of maximal injury (p < 0.001), left hippocampus (p < 0.001), and left thalamus (p = 0.02) at 48 h after brain injury. Administration of BW1003C87 15 min postinjury significantly reduced focal brain edema in the cortical area adjacent to the site of maximal injury (p < 0.02) and left hippocampus (p < 0.01), whereas magnesium chloride attenuated edema in left hippocampus (p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗