PubMed Health⌕ Search

Biomedical subjects

Bruce T Volpe

Publications and source records attributed to Bruce T Volpe.

29 records · Page 2Linked to original sources
PubMed2003

Microglial phagocytosis of dopamine neurons at early phases of apoptosis.

Transection of the medial forebrain bundle caused apoptosis of dopamine neurons in the rat substantia nigra. Immunohistochemical localization of activated microglia and tyrosine hydroxylase in the axotomized substantia nigra showed that activation of microglia was rapid and OX-6 (MHC-II marker)-positive and ED1 (lysosomal phagocytic marker)-positive microglia were apposed to structurally intact tyrosine hydroxylase-positive dopamine neurons, indicating microglial phagocytosis of degenerating dopamine neurons. The occurrence of microglial phagocytosis at early stages of apoptosis may indicate the evolution of apoptosis into an irreversible state. Alternatively, interventions that suppress early activation of microglia might lead to novel mechanisms for neuron protection.

Animals↗
PubMed2003

Reversal of thiamine deficiency-induced neurodegeneration.

Neurodegenerative diseases are characterized by abnormalities in oxidative processes, region-selective neuron loss, and diminished thiamine-dependent enzymes. Thiamine deficiency (TD) diminishes thiamine dependent enzymes, alters mitochondrial function, impairs oxidative metabolism, and causes selective neuronal death. In mice, the time course of TD-induced changes in neurons and microglia were determined in the brain region most sensitive to TD. Significant neuron loss (29%) occurred after 8 or 9 days of TD (TD8-9) and increased to 90% neuron loss by TD10-11. The number of microglia increased 16% by TD8 and by nearly 400% on TD11. Hemeoxygenase-1 (HO-1)-positive microglia were not detectable at TD8, yet increased dramatically coincident with neuron loss. To test the duration of TD critical for irrevocable changes, mice received thiamine after various durations of TD. Thiamine administration on TD8 blocked further neuronal loss and induction of HO-1-positive microglia, whereas other microglial changes persisted. Thiamine only partially reversed effects on TD9, and was ineffective on TD10-11. These studies indicate that irreversible steps leading to neuronal death and induction of HO-1-positive microglia occur on TD9. The results indicate that TD induces alterations in neurons. endothelial cells, and microglia contemporaneously. This model provides a unique paradigm for elucidating the molecular mechanisms involved in neuronal commitment to neuronal death cascades and contributory microglial activity.

Animals↗
PubMed2003

Robot-aided sensorimotor training in stroke rehabilitation.

The first groups to use robotic devices to enhance the sensorimotor experience of patients recovering from upper limb paralysis after stroke have generated encouraging information. Patient acceptance and staff enthusiasm for robot training at Burke--MIT is consistently high. Robot training data are consistent with other controlled studies showing that more activity leads to more motor improvement and decreased impairment. Therapists equipped with a robotic device can increase the amount and intensity of movement of the paralyzed limb without sacrificing time spent training complex functionally appropriate kinematics.

Arm↗
PubMed2002

Amyloid precursor protein gene disruption attenuates degeneration of substantia nigra compacta neurons following axotomy.

Our past work has shown that the C-terminal fragment of amyloid precursor protein (APP) translocated to the nucleus in neurons destined for delayed excitotoxic degeneration. To test whether nuclear APP fragments also play a role in the progressive loss of dopaminergic (DA) substantia nigra compacta (SNc) neurons, we performed unilateral medial forebrain bundle (MFB) transection on APP wild type (WT) and on mice with disruption of the APP gene (KO). In WT mice immunoreactivity for APP C-terminal, beta-amyloid and Alz90 epitopes appeared in the nuclei of axotomized DA neurons at 3 days post-lesion (dpl), persisted at 7 dpl and was absent in 14 dpl mice. APP N-terminal immunoreactivity was restricted to the cytosol at all time points, precluding the possibility of full length APP in the nucleus. Nuclear localization of APP epitopes was absent in neurons of the contralateral SNc or in neurons of the ipsilateral ventral tegmental area and SN reticulata. The presence of APP C-terminal and Alz90 domains was confirmed by Western blotting performed on the nuclear fraction of the SN ipsilateral to the axotomy. Quantitative morphometric analysis revealed that WT mice demonstrated earlier and more profound loss of tyrosine hydroxylase+SNc neurons than did KO mice. These data showed that a novel nuclear C-terminal fragment appeared coincident with SNc neuron degeneration, and that APP deficiency correlated with significant neuroprotection in vivo.

Amyloid beta-Protein Precursor↗
PubMed2002

17 beta-estradiol treatment retards excitotoxic delayed degeneration in substantia nigra reticulata neurons.

Estrogen treatment offers neuro-protection in animal experiments in which excitotoxic mechanisms destroy neurons. In a model of delayed neuronal degeneration that depends on excitotoxicity, we tested whether females had an altered susceptibility, and whether physiologic doses of estrogen administered after the brain insult would protect susceptible neurons. Females were ovariectomized, exposed to striatal-pallidal ibotenic acid injury that caused delayed degeneration of substantia nigra neurons, and treated with 17 beta -estradiol (30 microg, subcutaneously every other day, beginning 2 days after the striatal injury) or vehicle. At 6 and 8 days post lesion, the 17beta-estradiol treatment group maintained over 87 and 70% of control nigral neuron number, respectively. Physiologic levels of estrogen delivered days after the excitotoxic stress completely protected neurons in the substantia nigra reticulata 6 days post lesion and slowed degeneration 8 days post lesion.

Animals↗
PubMed2002

APP knockout attenuates microglial activation and enhances neuron survival in substantia nigra compacta after axotomy.

Focal microglial activation and progressive dopaminergic neurodegeneration in substantia nigra compacta (SNc) have characterized Parkinson's disease (PD). We have hypothesized that the microglial response may be provoked by molecular signals from chronically stressed SNc neurons. To test whether amyloid precursor protein (APP) could serve as such a signal, we evaluated microglial activation in SN after unilateral transection of the medial forebrain bundle (MFB) in mice either wild-type (WT) or null (KO) for APP. WT and KO mice displayed comparable microglial response at the MFB transection site. In WT mice microglial activation was first apparent in the ipsilateral SN at 3 days postlesion (dpl), marked by morphological change and increased isolectin immunoreactivity. The microglial response intensified at 7 dpl and persisted in the medial nigra through 14 dpl. In contrast, in KO mice activated microglia appeared predominantly at 7 dpl, with little activation at 3 dpl and none at 14 dpl. Neuron number in affected WT SNc at 14 dpl was significantly reduced compared with loss in affected KO SNc. The delayed and limited local microglial activation and increased neuron survival in response to distal axotomy of SNc neurons in APP KO mice are consistent with the important role APP in neuronal stress responses in vivo.

Amyloid beta-Protein Precursor↗
PubMed2002

Marked dopaminergic cell loss subsequent to developmental, intranigral expression of glial cell line-derived neurotrophic factor.

Glial cell line-derived neurotrophic factor (GDNF) shows potent neuroprotective as well as neurorestorative actions on the adult neurons impacted in animal models of Parkinson's disease (PD). Long-term pharmaco-physiological effects of GDNF on developing dopaminergic (DA) neurons have not yet been explored because of technical difficulties in producing prolonged cell type-specific delivery of this neurotrophic factor in mammalian embryonic brain. The current studies used our previously characterized 9.0-kb tyrosine hydroxylase promoter to produce transgenic mice with neuronal cell type-specific expression of GDNF in substantia nigra pars compacta (SNc) and locus coeruleus (LC). These mice were used to test the parsimonious hypothesis that increased developmental expression of GDNF in SNc and LC would significantly enhance the number of postmitotic adult neurons. To our surprise, adult transgenic mice carrying the TH9.0kb-GDNF hybrid gene showed dramatic reductions in both the numbers and the volumes of SNc-DA and LC-noradrenergic (NA) neurons by quantitative morphometric analysis. The decrease in the number of DA neurons was apparent as early as postnatal day 2, the period before the major naturally occurring apoptotic cell death in midbrain. Aged transgenic mice exhibited no further significant deficits in motor behaviors. These data suggest that continuous, early developmental GDNF expression exerts physiological effects on newly differentiated, immature dopamine neurons that differ from those observed on more mature and adult DA neurons. Further elucidation of the mechanisms underlying differential GDNF actions will greatly improve the pharmacological efficacy of GDNF in fetal neural transplantation as well as adult neuronal gene therapy in PD patients.

Aging↗
PubMed2002

Robotics in the rehabilitation treatment of patients with stroke.

Stroke is the leading cause of permanent disability despite continued advances in prevention and novel interventional treatments. Post-stroke neuro-rehabilitation programs teach compensatory strategies that alter the degree of permanent disability. Robotic devices are new tools for therapists to deliver enhanced sensorimotor training and concentrate on impairment reduction. Results from several groups have registered success in reducing impairment and increasing motor power with task-specific exercise delivered by the robotic devices. Enhancing the rehabilitation experience with task-specific repetitive exercise marks a different approach to the patient with stroke. The clinical challenge will be to streamline, adapt, and expand the robot protocols to accommodate healthcare economies, to determine which patients sustain the greatest benefit, and to explore the relationship between impairment reduction and disability level. With these new tools, therapists will measure aspects of outcome objectively and contribute to the emerging scientific basis of neuro-rehabilitation.

Bionics↗
PubMed2002

Assessing the motor status score: a scale for the evaluation of upper limb motor outcomes in patients after stroke.

The Motor Status Scale (MSS) measures shoulder, elbow (maximum score = 40), wrist, hand, and finger movements (maximum score = 42), and expands the measurement of upper extremity impairment and disability provided by the Fugl-Meyer (FM) score. This work examines the interrater reliability and criterion validity of the MSS performed in patients admitted to a rehabilitation hospital 21 +/- 4 days after stroke. Using the MSS and the FM, 7 occupational therapists masked to each other's judgments, evaluated 12 consecutive patients with stroke. Two therapists evaluated 6 additional patients on consecutive days. Intraclass correlation coefficients were significant for each group of raters for the shoulder/elbow and for the wrist/band (P < 0.0001); test-retest measures were also significant for the shoulder/elbow (Pearson correlation coefficient r = 0.99, P < 0.004) and for the wrist/hand (Pearson correlation coefficient r = 0.99, P < 0.003). The internal item consistency for the overall MSS was significant (Cronbach alpha = 0.98, P < 0.0001). Finally the correlation between the MSS and the FM (R2 = 0.964) was significant (P < 0.0001). The MSS affords a reliable and valid assessment of upper limb impairment and disability following stroke.

Disability Evaluation↗
PubMedDate not supplied

Motions or muscles? Some behavioral factors underlying robotic assistance of motor recovery.

Robotics and related technologies have begun to realize their promise to improve the delivery of rehabilitation therapy. However, the mechanism by which they enhance recovery remains unclear. Ultimately, recovery depends on biology, yet the details of the recovery process remain largely unknown; a deeper understanding is important to accelerate refinements of robotic therapy or suggest new approaches. Fortunately, robots provide an excellent instrument platform from which to study recovery at the behavioral level. This article reviews some initial insights about the process of upper-limb behavioral recovery that have emerged from our work. Evidence to date suggests that the form of therapy may be more important than its intensity: muscle strengthening offers no advantage over movement training. Passive movement is insufficient; active participation is required. Progressive training based on measures of movement coordination yields substantially improved outcomes. Together these results indicate that movement coordination rather than muscle activation may be the most appropriate focus for robotic therapy.

Behavior↗