The Promise of Neuroprotective Agents in Parkinson’s Disease

Parkinson’s disease (PD) is characterized by loss of dopamine neurons in the substantia nigra of the brain. Since there are limited treatment options for PD, neuroprotective agents are currently being tested as a means to slow disease progression. Agents targeting oxidative stress, mitochondrial dysfunction, and inflammation are prime candidates for neuroprotection. This review identifies Rasagiline, Minocycline, and creatine, as the most promising neuroprotective agents for PD, and they are all currently in phase III trials. Other agents possessing protective characteristics in delaying PD include stimulants, vitamins, supplements, and other drugs. Additionally, combination therapies also show benefits in slowing PD progression. The identification of neuroprotective agents for PD provides us with therapeutic opportunities for modifying the course of disease progression and, perhaps, reducing the risk of onset when preclinical biomarkers become available

Septohippocampal Neuromodulation Improves Cognition after Traumatic Brain Injury.

Traumatic brain injury (TBI) often results in persistent attention and memory deficits that are associated with hippocampal dysfunction. Although deep brain stimulation (DBS) is used to treat neurological disorders related to motor dysfunction, the effectiveness of stimulation to treat cognition remains largely unknown. In this study, adult male Harlan Sprague-Dawley rats underwent a lateral fluid percussion or sham injury followed by implantation of bipolar electrodes in the medial septal nucleus (MSN) and ipsilateral hippocampus. In the first week after injury, there was a significant decrease in hippocampal theta oscillations that correlated with decreased object exploration and impaired performance in the Barnes maze spatial learning task. Continuous 7.7 Hz theta stimulation of the medial septum significantly increased hippocampal theta oscillations, restored normal object exploration, and improved spatial learning in injured animals. There were no benefits with 100 Hz gamma stimulation, and stimulation of sham animals at either frequency did not enhance performance. We conclude, therefore, that there was a theta frequency-specific benefit of DBS that restored cognitive function in brain-injured rats. These data suggest that septal theta stimulation may be an effective and novel neuromodulatory therapy for treatment of persistent cognitive deficits following TBI

Septohippocampal Neuromodulation Improves Cognition after Traumatic Brain Injury

Traumatic brain injury (TBI) often results in persistent attention and memory deficits that are associated with hippocampal dysfunction. Although deep brain stimulation (DBS) is used to treat neurological disorders related to motor dysfunction, the effectiveness of stimulation to treat cognition remains largely unknown. In this study, adult male Harlan Sprague-Dawley rats underwent a lateral fluid percussion or sham injury followed by implantation of bipolar electrodes in the medial septal nucleus (MSN) and ipsilateral hippocampus. In the first week after injury, there was a significant decrease in hippocampal theta oscillations that correlated with decreased object exploration and impaired performance in the Barnes maze spatial learning task. Continuous 7.7 Hz theta stimulation of the medial septum significantly increased hippocampal theta oscillations, restored normal object exploration, and improved spatial learning in injured animals. There were no benefits with 100 Hz gamma stimulation, and stimulation of sham animals at either frequency did not enhance performance. We conclude, therefore, that there was a theta frequency-specific benefit of DBS that restored cognitive function in brain-injured rats. These data suggest that septal theta stimulation may be an effective and novel neuromodulatory therapy for treatment of persistent cognitive deficits following TBI

Women's decision making about the use of natural health products at menopause : a needs assessment and patient decision aid

Objective: To identify the decision-making needs of women about the use of natural health products (NHP) at menopause and to develop a decision aid responsive to their needs. Design: A qualitative study using focus groups, key informant interviews and group consultation. Content analysis was guided by the Ottawa Decision Support Framework. Methods: Six focus groups with menopausal women aged 45 to 64 ( n = 40) and key informant interviews ( n = 15; physicians, nurses, women's advocacy group, NHP stores owners, pharmacists, policy makers) were conducted in two Canadian cities. Two groups of menopausal women ( n = 11) were consulted to obtain feedback on the acceptability of the new patient decision aid. Results: The most common difficult decisions identified by women were: whether or not to take NHP; which NHP to choose; and whether or not to take anything for menopausal symptoms. In addition, key informants identified the challenge of choosing between hormone therapy and NHP for menopausal symptoms. The main sources of difficulty in making these decisions were the following: ( 1) inadequate knowledge and unrealistic expectations associated with NHP; ( 2) closed mindedness of physicians to discussion about NHP; ( 3) conflicting opinions of others; ( 4) inadequate resources to support NHP decision-making ( e. g., information, finances, time); and ( 5) menopausal symptoms interfering with decision-making ( e. g., lack of sleep due to hot flashes). To facilitate decision making, participants suggested the need for information about available choices, tighter regulation of NHP by the government, and access to health professionals conversant in NHP and medical options. The patient decision aid was developed according to the International Patient Decision Aid Standards and based on women's identified needs. Women described the aid as easy to understand and useful for considering the decisions about NHP. Conclusions: Middle-age women reported difficulty when facing decisions about the use of NHP. Many sources of difficulty could be addressed in the patient decision aid. Subsequent studies should evaluate the effect of this decision aid on the decision-making process of women

Targeted Gene Inactivation of Calpain-1 Suppresses Cortical Degeneration Due to Traumatic Brain Injury and Neuronal Apoptosis Induced by Oxidative Stress*

Calpains are calcium-regulated cysteine proteases that have been implicated in the regulation of cell death pathways. Here, we used our calpain-1 null mouse model to evaluate the function of calpain-1 in neural degeneration following a rodent model of traumatic brain injury. In vivo, calpain-1 null mice show significantly less neural degeneration and apoptosis and a smaller contusion 3 days post-injury than wild type littermates. Protection from traumatic brain injury corroborated with the resistance of calpain-1 neurons to apoptosis induced by oxidative stress. Biochemical analysis revealed that caspase-3 activation, extracellular calcium entry, mitochondrial membrane permeability, and release of apoptosis-inducing factor from mitochondria are partially blocked in the calpain-1 null neurons. These findings suggest that the calpain-1 knock-out mice may serve as a useful model system for neuronal protection and apoptosis in traumatic brain injury and other neurodegenerative disorders in which oxidative stress plays a role