Hippocampal damage and cytoskeletal disruption resulting from impaired energy metabolism

To determine if impaired energy metabolism might contribute to some aspects of Alzheimer disease (AD), including the vulnerability of the CA1 region of the hippocampal formation and the altered cytoskeleton evident in neurofibrillary tangles, we examined the effects of metabolic poisons on neuronal damage and cytoskeletal disruption in the hippocampal formation. Intrahippocampal injection of 3-nitropropionic acid (3-NP) and malonic acid resulted in neuronal death, particularly in CA1. Cytoskeletal disruption included loss of dendritic MAP2, but sparing of axonal τ. MK-801 (a noncompetitive NMDA receptor antagonist) did not atenuate the lesions produced by intrahippocampal injection of malonate. MK-801, however, was effective against intrastriatal malonate. Acute systemic 3-NP resulted in neuronal damage and cytoskeletal disruption in the CA1 region of the hippocampal formation, including an extensive loss of MAP2 immuno-reactivity, but sparing of τ. The neuronal loss in CA1 was delayed as compared to striatum. Chronic intraventricular infusion of 3-NP produced a different pattern of neuronal damage. Loss of τ-1 immuno-reactivity was observed in CA3 and CA1 s. oriens, whereas MAP2 immunostaining was preserved. These results demonstrate that chronic and acute administration of metabolic inhibitors produce distinct patterns of neuronal damage and cytoskeletal disruption. The results further suggest a differential involvement of the NMDA receptor in malonate-induced neuronal damage in striatum as compared to the hippocampus. The pattern of neuronal damage and cytoskeletal disruption observed following acute metabolic impairment resembled some aspects of neurofibrillary pathology in AD, but did not result in τ hyperphosphorylation.     

Executive and compensatory memory retraining in traumatic brain injury

A controlled treatment outcome study was conducted comparing the efficacy of memory remediation treatment with no treatment on traumatic brain-injury patients. The memory remediation treatment consisted of both compensatory and executive training skills and was delivered 6 hours weekly over a 2 1/2-week period. Six subjects in the treatment group and 6 subjects in the control group were matched on WAIS-R FSIQ scores, pre-test memory scores and age. Pre-and post-test measures were obtained for both groups on a paragraph memory task. A significant difference was demonstrated between the treatment and control post-test memory scores. The experimental group significantly improved memory scores beyond that of the control group, suggesting that memory remediation is effective for head-injury patients with memory deficits. Discussion of findings and suggestions for further investigation are presented.     

Percutaneous bone marrow grafting of fractures and bony defects. An experimental study in rabbits

Since bone marrow has been shown to contain osteoprogenitor cells, an experiment was devised to test its effects when injected percutaneously into osteotomies and 2-cm bony defects produced in rabbit radii. The parameters tested included callus volume, breaking load, tensile strength, and cross-sectional area of callus at the fracture or bony defect site. At two weeks postgrafting callus volume was significantly higher (p less than 0.01) in the grafted radii than in the contralateral saline controls. By four weeks all four parameters were significantly greater in the bone marrow grafted radii than in the contralateral saline controls. Serial radiographs and histology confirm this advanced fracture healing in the grafted bones. The earlier and more abundant callus, at the bone marrow grafted sites, was felt to provide earlier and greater stability, resulting in decreased early healing time when contrasted with the saline controls. Similarly, the bony defects that were grafted with bone marrow united by a bony bridge, whereas the saline controls did not. Percutaneous bone marrow grafting is a simple semi-invasive technique that may have potential clinical applications.     

Multicystic peritoneal mesothelioma in a 29 year old male

A case of multicystic peritoneal mesothelioma in a 29 year old white male is reported. This is the second reported case of cystic peritoneal mesothelioma in a male and the first case of cystic mesothelioma reported in Australia. Clinical, histopathologic and ultrastructural findings are discussed together with a review of previous cases.     

Superior humeral dislocation. A complication following decompression and debridement for rotator cuff tears

Very large rotator cuff tears may be surgically irreparable and under such circumstances debridement of the edges of the cuff and bursal decompression may relieve pain. In this paper, four cases are described of the development of superior migration of the humeral head following a debridement and bural decompression. In all four patients attempts were made to repair the rotator cuff. In each case the repair failed and the humeral head migrated. Two of the patients had the humeral head replaced because of a fracture; in these patients the prosthesis displaced upwards. This serious complication may follow debridement and release of the subacromial bursa when rotator cuff repair cannot be achieved. In the correction of superior humeral migration, reestablishment of the roof of the bursa was carried out in two cases. This procedure appears effective and may be considered in the future for such cases.     

Structural and histochemical features of the avian blood-brain barrier

We have investigated the structural and histochemical features of the blood-brain barrier (b-bb) in both adults and embryos of chicken (Gallus domesticus, White Leghorn) and quail (Corturnix coturnix japonica). We found that brain endothelial cells of both species are characterized structurally by tight junctions, a low density of pinocytotic vesicles, and a moderately elevated density of mitochondria. Both alkaline phosphatase and butyryl cholinesterase were found in adult quail brain capillaries, but only alkaline phosphatase was found in adult chick brain capillaries. Aromatic amino acid decarboxylase was not found in brain capillaries of either species. In the chick embryo alkaline phsophatase appeared during the time when b-bb matures functionally; i.e., during the third week of development. However, an elevation in mitochondrial density was not apparent until after hatching. In the quail, alkaline phosphatase and butyrl cholinesterase appeared during the last week of embryonic development. By 2 days posthatching the structural characteristics of the brain capillaries were similar to those in the adult.     

Spatial learning impairments in rats with selective immunolesion of the forebrain cholinergic system.

A monoclonal antibody to the low-affinity NGF receptor, 192 IgG, coupled to a cytotoxin, saporin, was recently introduced as an efficient selective neurotoxin for the NGFr-bearing cholinergic neurones in the rat basal forebrain. In the present study we report that an intracerebroventricular injection of this 192 IgG-saporin conjugate induces a severe, long-lasting spatial learning impairment, as assessed in the Morris water-maze task. This behavioural impairment was associated with 65-90% depletion of choline acetyltransferase activity (ChAT) in the hippocampus and cortex. ChAT activity associated with other cholinergic neurone systems in the brain (striatum, mesencephalon, spinal cord), was left virtually unaffected. This new immunotoxin holds great promise as a tool for selective and efficient lesions of the forebrain cholinergic system in functional and behavioural studies.