A Multidimensional Assessment of Activities of Daily Living, Mental Status, Communication, and Social Abilities Among Older Adults in Shenzhen, China: Cross-Sectional Study.

BACKGROUND: China is facing a rapidly expanding aging population. Insights into the health status of older adults are of great significance for health resource allocation and health care provision to this population. OBJECTIVE: With the goal of providing a comprehensive understanding of the health status of older adults and to inform potential interventions, we investigated the level of disability and identified risk factors associated with disability among the older population (aged ≥60 years) living in China. METHODS: A total of 8467 older adults living in the Chinese city of Shenzhen were enrolled in this cross-sectional study. We used a multidimensional ability assessment survey, which assessed their activities of daily living (ADL; including eating, bathing, grooming, dressing, defecation control, urination control, using a toilet unaided, transfer, flat-ground walking, stair activity), mental status (including cognitive function, aggressive behavior, depression symptoms), sensory and communication (including consciousness level, vision, hearing, communication), and social participation (including living, working, time/space orientation, distinguish persons, social communication) abilities. The impact of demographic risk factors on ability levels was analyzed using ordinal logistic regression. The correlations between the four dimensions of ability mentioned above were analyzed using Spearman correlation analysis. RESULTS: A total of 7766 participants were effectively assessed. The participants' average age was 70.64 (SD 8.46) years comprising 56.53% females. The overall ability level was classified as mildly, moderately, and severely impaired for 27.57% (n=2141), 2.83% (n=220), and 4.28% (n=332) of the 7766 participants, respectively. With increasing age, the proportion of impaired participants increased from 17.62% (365/2071) in the age group 60-64 years to 91.3% (253/277) in the age group above 90 years (P<.001), corresponding to an approximate 10% rise for every 5-year age increment. The odds of having more severe overall ability impairment in females was 1.15 times that in males (odds ratio [OR] 1.15, 95% CI 1.04-1.28). Participants who were divorced or widowed had a higher risk of more severe overall ability impairment than those currently married (OR 1.98, 95% CI 1.68-2.33). Participants living with nonrelatives had an increased risk of more severe overall ability impairment than those living alone (OR 2.38, 95% CI 1.46-3.91). Higher education level was a protective factor of overall ability impairment (college degree or above: OR 0.32, 95% CI 0.24-0.42). The four dimensions of ability assessed were significantly correlated; a low score for ADL was significantly correlated with poorer mental status, sensory and communication, and social participation (all P<.001). CONCLUSIONS: The proportion of disability among Chinese older adults increases with age, being female, having lower education levels, being divorced or widowed, and living with nonrelatives. Impairment in ADL ability is significantly correlated with poor mental status, social participation, and sensory and communication abilities. A holistic approach to improving the health of the older population is recommended in China.

The epidemiology of epilepsy in older adults: A narrative review by the ILAE Task Force on Epilepsy in the Elderly.

In an aging world, it is important to know the burden of epilepsy affecting populations of older persons. We performed a selective review of epidemiological studies that we considered to be most informative, trying to include data from all parts of the world. We emphasized primary reports rather than review articles. We reviewed studies reporting the incidence and prevalence of epilepsy that focused on an older population as well as studies that included a wider age range if older persons were tabulated as a subgroup. There is strong evidence that persons older than approximately 60 years incur an increasing risk of both acute symptomatic seizures and epilepsy. In wealthier countries, the incidence of epilepsy increases sharply after age 60 or 65 years. This phenomenon was not always observed among reports from populations with lower socioeconomic status. This discrepancy may reflect differences in etiologies, methods of ascertainment, or distribution of ages; this is an area for more research. We identified other areas for which there are inadequate data. Incidence data are scarcer than prevalence data and are missing for large areas of the world. Prevalence is lower than would be expected from cumulative incidence, possibly because of remissions, excess mortality, or misdiagnosis of acute symptomatic seizures as epilepsy. Segmentation by age, frailty, and comorbidities is desirable, because "epilepsy in the elderly" is otherwise too broad a concept. Data are needed on rates of status epilepticus and drug-resistant epilepsy using the newer definitions. Many more data are needed from low-income populations and from developing countries. Greater awareness of the high rates of seizures among older adults should lead to more focused diagnostic efforts for individuals. Accurate data on epilepsy among older adults should drive proper allocation of treatments for individuals and resources for societies.

Management of epilepsy in older adults: A critical review by the ILAE Task Force on Epilepsy in the elderly.

Older adults represent a highly heterogeneous population, with multiple diverse subgroups. Therefore, an individualized approach to treatment is essential to meet the needs of each unique subgroup. Most comparative studies focusing on treatment of epilepsy in older adults have found that levetiracetam has the best chance of long-term seizure freedom. However, there is a lack of studies investigating other newer generation antiseizure medications (ASMs). Although a number of randomized clinical trials have been performed on older adults with epilepsy, the number of participants studied was generally small, and they only investigated short-term efficacy and tolerability. Quality of life as an outcome is often missing but is necessary to understand the effectiveness and possible side effects of treatment. Prognosis needs to move beyond the focus on seizure control to long-term patient-centered outcomes. Dosing studies with newer generation ASMs are needed to understand which treatments are the best in the older adults with different comorbidities. In particular, more high-level evidence is required for older adults with Alzheimer's disease with epilepsy and status epilepticus. Future treatment studies should use greater homogeneity in the inclusion criteria to allow for clearer findings that can be comparable with other studies to build the existing treatment evidence base.

Preferences and User Experiences of Wearable Devices in Epilepsy: A Systematic Review and Mixed-Methods Synthesis.

BACKGROUND AND OBJECTIVES: To examine the preferences and user experiences of people with epilepsy and caregivers regarding automated wearable seizure detection devices. METHODS: We performed a mixed-methods systematic review. We searched electronic databases for original peer-reviewed publications between January 1, 2000, and May 26, 2021. Key search terms included "epilepsy," "seizure," "wearable," and "non-invasive." We performed a descriptive and qualitative thematic analysis of the studies included according to the technology acceptance model. Full texts of the discussion sections were further analyzed to identify word frequency and word mapping. RESULTS: Twenty-two observational studies were identified. Collectively, they comprised responses from 3,299 participants including patients with epilepsy, caregivers, and healthcare workers. Sixteen studies examined user preferences, 5 examined user experiences, and 1 examined both experiences and preferences. Important preferences for wearables included improving care, cost, accuracy, and design. Patients desired real-time detection with a latency of ≤15 minutes from seizure occurrence, along with high sensitivity (≥90%) and low false alarm rates. Device-related costs were a major factor for device acceptance, where device costs of <$300 USD and a monthly subscription fee of <$20 USD were preferred. Despite being a major driver of wearable-based technologies, sudden unexpected death in epilepsy was rarely discussed. Among studies evaluating user experiences, there was a greater acceptance toward wristwatches. Thematic coding analysis showed that attitudes toward device use and perceived usefulness were reported consistently. Word mapping identified "specificity," "cost," and "battery" as key single terms and "battery life," "insurance coverage," "prediction/detection quality," and the effect of devices on "daily life" as key bigrams. DISCUSSION: User acceptance of wearable technology for seizure detection was strongly influenced by accuracy, design, comfort, and cost. Our findings emphasize the need for standardized and validated tools to comprehensively examine preferences and user experiences of wearable devices in this population using the themes identified in this study. Greater efforts to incorporate perspectives and user experiences in developing wearables for seizure detection, particularly in community-based settings, are needed. TRIAL REGISTRATION INFORMATION: PROSPERO Registration CRD42020193565.

New-onset epilepsy in the elderly.

People who are 60 years old and older have the highest incidence of developing new-onset epilepsy. The increase of the ageing population has resulted in a greater number of patients with new-onset epilepsy or at risk of developing the condition. Previously published review articles regarding epilepsy in older patients have had a broad focus, including people who were diagnosed with epilepsy in their childhood or middle age. The present review focuses on the causes, treatment, prognosis and psychosocial impact of new-onset epilepsy in people aged ≥60 years. Following a search of the medical electronic databases and relevant references, we identified 22 studies overall that met the inclusion criteria. Only four randomized clinical trials (RCTs) were identified that compared different antiepileptic drug treatments in this population, demonstrating that newer-generation antiepileptic drugs (e.g. lamotrigine and levetiracetam) were generally better tolerated. One uncontrolled study provided promising evidence of good outcomes and safety for surgical resection as a treatment for people with uncontrolled seizures. Five studies reported that people ≥60 years with new-onset epilepsy have significant cognitive impairments (e.g. memory loss) and psychological issues including depression, anxiety and fatigue. We found that there is limited evidence to guide treatment in people with Alzheimer's disease and epilepsy. The specific features of new-onset epilepsy in this target population significantly influences the choice of treatment. Cognitive and psychiatric screening before treatment may be useful for management. Two studies with proposed guidelines were identified but no formal clinical practice guidelines exist for this special population to assist with appropriate management. There is a need for more RCTs that investigate effective treatments with limited side effects. More research studies on the psychosocial effects of new-onset epilepsy, and long-term outcomes, for people aged ≥60 years are also required.

Older people and knowledge of epilepsy: GPs can help.

BACKGROUND: Epilepsy is a common neurological disease with a high prevalence in people aged 65 years or older. Therefore, an understanding of the disease is important. The objective of this article was to determine older people's knowledge of epilepsy. METHODS: Electronic or paper-based surveys were completed by people aged 65 years and older. RESULTS: Five hundred and seventy-two surveys were completed, including 100 from people with epilepsy. Those with epilepsy had relatively poor knowledge of their condition, but they answered some questions significantly more correctly than participants without epilepsy. The main predictor of knowledge was clear information from a health professional. Two-thirds of those with epilepsy had their condition managed by a general practitioner. DISCUSSION: Older people with epilepsy need more information on their condition to facilitate better care management.

Management of post-traumatic epilepsy: An evidence review over the last 5 years and future directions.

Post-traumatic epilepsy (PTE) is a relatively underappreciated condition that can develop as a secondary consequence following traumatic brain injury (TBI). The aim of this rapid evidence review is to provide a synthesis of existing evidence on the effectiveness of treatment interventions for the prevention of PTE in people who have suffered a moderate/severe TBI to increase awareness and understanding among consumers. Electronic medical databases (n = 5) and gray literature published between January 2010 and April 2015 were searched for studies on the management of PTE. Twenty-two eligible studies were identified that met the inclusion criteria. No evidence was found for the effectiveness of any pharmacological treatments in the prevention or treatment of symptomatic seizures in adults with PTE. However, limited high-level evidence for the effectiveness of the antiepileptic drug levetiracetam was identified for PTE in children. Low-level evidence was identified for nonpharmacological interventions in significantly reducing seizures in patients with PTE, but only in a minority of cases, requiring further high-level studies to confirm the results. This review provides an opportunity for researchers and health service professionals to better understand the underlying pathophysiology of PTE to develop novel, more effective therapeutic targets and to improve the quality of life of people with this condition.

Guidance for community-based caregivers in assisting people with moderate to severe traumatic brain injury with transfers and manual handling: evidence and key stakeholder perspectives.

Adults with moderate to severe traumatic brain injury (TBI) rely on assistance from paid and unpaid caregivers upon return to the community. An inability to move independently makes these adults highly dependent on caregivers for transfers and manual handling tasks. Evidence-based guidelines are therefore important to ensure that caregivers and people in the community are protected and that practices are standard and consistent. This study commenced with a rapid review of evidence-based recommendations between 2000 and 2015 pertaining to transfers and manual handling in people with TBI; and ended with a structured stakeholder dialogue that reflected upon this evidence and gathered perspectives on how to address key issues in community-based manual handling following TBI. Three relevant guidelines were identified, providing nine recommendations encompassing assessment of the person's ability to assist caregivers, manual handling and appropriate equipment use. Due to the low number of recommendations and low level of supporting evidence, these recommendations alone could not provide comprehensive guidance. Three systematic reviews and two primary studies were also identified, and these suggest that comprehensive training programmes in transfers and manual handling tasks are effective. Further to this, a structured stakeholder dialogue was conducted, which revealed six major themes - (i) comprehensive risk assessment, (ii) presence of two caregivers, (iii) provision of training, (iv) home environment modification, (v) equipment, and (vi) policy implementation context. Recommendations for health professionals include providing information packs to caregivers, risk assessment and mitigation for those at high risk, and strategies to prevent and minimise injury in caregivers. Development of comprehensive guidance for caregivers in transfers and manual handling in people with moderate to severe TBI living in the community is a hidden but important priority.

Management of Spasticity in Moderate and Severe Traumatic Brain Injury: Evaluation of Clinical Practice Guidelines.

INTRODUCTION: Moderate to severe traumatic brain injury (TBI) can result in development of spasticity, which adversely affects function and quality of life. Given the foundation of optimal clinical practice is use of the best available evidence, we aimed to identify, describe, and evaluate methodological quality of evidence-based spasticity clinical practice guidelines (CPGs). METHODS: A comprehensive search for CPGs encompassed electronic databases and online sources. Eligible CPGs were evaluated using the validated Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. RESULTS: Five CPGs were eligible for review; 2 were specific to acquired brain injury and 1 to TBI. The 3 brain injury-specific CPGs contained 423 recommendations overall, but only 8 spasticity recommendations. On the basis of AGREE appraisals, all CPGs performed well in the areas of reporting scope and purpose; clearly presenting recommendations; including various stakeholders in the CPG development process; and reporting conflict of interest. However, only one CPG performed adequately on describing facilitators and barriers to implementation, advice, and tools on how to implement recommendations and provision of audit criteria. Intraclass correlation coefficient (ICC) for agreement between raters showed high agreement (ICC > 0.80) for most guidelines. CONCLUSION: Given the unique etiological features and treatment challenges associated with managing spasticity after TBI, more TBI-specific spasticity CPGs are required. These should incorporate information on the facilitators and barriers to implementation, advice on implementing recommendations, and audit criteria.

The experience of discharge for patients with an acquired brain injury from the inpatient to the community setting: A qualitative review.

BACKGROUND: Discharge planning for patients with an acquired brain injury (ABI) is considered best practice for assisting the patient and caregiver to successfully transition from hospital to home and is complex because of the long-term care and support needs of the patient. This review aimed to describe and synthesize the perspectives of patients with ABI and their family/caregivers on the transition from hospital to home to better understand opportunities to optimize the process. METHODS: Electronic medical databases (n = 5) and grey literature published between January-May 2015 were searched to identify qualitative studies on the experience of transition from the hospital to home setting following ABI. Relevant studies were appraised and narratively synthesized. RESULTS: Nine eligible studies that met the inclusion criteria were identified. Two major themes were identified-Engagement and Support. Three underlying sub-themes-poor communication, limited participation and disorganized arrangements for support services-were identified as key contributors to an unsatisfactory experience for patients and their family/caregivers. CONCLUSION: The transition for patients with an ABI and their family/caregivers was characterized as fragmented and unsatisfactory for supporting a successful return home. This review highlights the importance of tailored education and involvement of the patient and their family/caregiver to increase readiness for returning home and reduce unplanned re-admissions.

Vitamin E supplementation and mortality in healthy people: a meta-analysis of randomised controlled trials.

PURPOSE: To evaluate the effect of oral vitamin E supplementation on all-cause mortality in apparently healthy people. METHODS: A systematic review and meta-analysis was conducted on randomised controlled trials (RCTs) with ≥ 6 months of follow up investigating the effect of vitamin E supplementation on healthy adults in developed countries. Electronic databases (MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials) and reference lists of trial reports were searched for RCTs published between 1966 and June 2012. Three investigators assessed eligibility of identified trials. Disagreements were resolved by consensus. Two investigators independently extracted data according to the criteria. RESULTS: There were 18 RCTs identified with 142,219 apparently healthy participants (71,116 in vitamin E intervention groups and 71,103 in control groups) that were included in the final analysis. Fixed effect and random effects analysis of the 18 trials revealed that supplementation with vitamin E was not associated with all-cause mortality (relative risk 1.01, 95% confidence interval 0.97 - 1.05, p = 0.65). Subgroup analyses by type of vitamin E (natural or synthetic), dose or duration of exposure, study design or quality, and pre-specified mortality outcome showed no association with all-cause mortality. CONCLUSIONS: The evidence from pooled analysis of 18 randomised controlled trials undertaken in apparently healthy people shows no effect of vitamin E supplementation at a dose of 23-800 IU/day on all-cause mortality.

Quality of guidelines for cognitive rehabilitation following traumatic brain injury.

INTRODUCTION: Cognitive rehabilitation following traumatic brain injury can aid in optimizing function, independence, and quality of life by addressing impairments in attention, executive function, cognitive communication, and memory. This study aimed to identify and evaluate the methodological quality of clinical practice guidelines for cognitive rehabilitation following traumatic brain injury. METHODS: Systematic searching of databases and Web sites was undertaken between January and March 2012 to identify freely available, English language clinical practice guidelines from 2002 onward. Eligible guidelines were evaluated using the validated Appraisal of Guidelines for Research and Evaluation II instrument. RESULTS: The 11 guidelines that met inclusion criteria were independently rated by 4 raters. Results of quality appraisal indicated that guidelines generally employed systematic search and appraisal methods and produced unambiguous, clearly identifiable recommendations. Conversely, only 1 guideline incorporated implementation and audit information, and there was poor reporting of processes for formulating, reviewing, and ensuring currency of recommendations and incorporating patient preferences. Intraclass correlation coefficients for agreement between raters showed high agreement (intraclass correlation coefficient > 0.80) for all guidelines except for 1 (moderate agreement; intraclass correlation coefficient = 0.76). CONCLUSION: Future guidelines should address identified limitations by providing implementation information and audit criteria, along with better reporting of guideline development processes and stakeholder engagement.

Pharmacotherapies for obesity: past, current, and future therapies.

Past therapies for the treatment of obesity have typically involved pharmacological agents usually in combination with a calorie-controlled diet. This paper reviews the efficacy and safety of pharmacotherapies for obesity focusing on drugs approved for long-term therapy (orlistat), drugs approved for short-term use (amfepramone [diethylpropion], phentermine), recently withdrawn therapies (rimonabant, sibutamine) and drugs evaluated in Phase III studies (taranabant, pramlintide, lorcaserin and tesofensine and combination therapies of topiramate plus phentermine, bupropion plus naltrexone, and bupropion plus zonisamide). No current pharmacotherapy possesses the efficacy needed to produce substantial weight loss in morbidly obese patients. Meta-analyses support a significant though modest loss in bodyweight with a mean weight difference of 4.7 kg (95% CI 4.1 to 5.3 kg) for rimonabant, 4.2 kg (95% CI 3.6 to 4.8 kg) for sibutramine and 2.9 kg (95% CI 2.5 to 3.2 kg) for orlistat compared to placebo at ≥12 months. Of the Phase III pharmacotherapies, lorcaserin, taranabant, topiramate and bupropion with naltrexone have demonstrated significant weight loss compared to placebo at ≥12 months. Some pharmacotherapies have also demonstrated clinical benefits. Further studies are required in some populations such as younger and older people whilst the long term safety continues to be a major consideration and has led to the withdrawal of several drugs.

Smoking cessation-recent advances.

BACKGROUND: Smoking continues to be a major contributor to the burden of disease across the world although there has been a decrease in some developed countries such as USA and Australia. In countries of South-East Asia with a high prevalence of smoking, the incidence of tobacco-related diseases will continue to increase. METHODS: We reviewed the literature in relation to the pharmacology of nicotine, the measures used to determine the efficacy of anti-smoking therapies, and the randomised controlled trials and systematic reviews of pharmacotherapies published between 2004 and 2010. We focused primarily on the three first line therapies that are currently available: nicotine replacement therapy (NRT), bupropion and varenicline. RESULTS: Randomised controlled trials and meta-analyses have demonstrated that single therapy with either NRT, bupropion or varenicline are all more effective than placebo for smoking cessation. Abstinence rates for monotherapies varies from 13.3% to 19% for NRT compared to 7.5% to 14% for placebo, 19% to 19.7% for bupropion versus 10.9% to 11% for placebo and 25.5% to 25.6% for varenicline versus 11.2% to 14.8% for placebo. Of current therapies varenicline appears to be more effective at achieving abstinence. Some combination therapies with one or two formulations of NRT or NRT plus bupropion have demonstrated superior results to monotherapy. To date there are no randomised controlled trials of varenicline in combination with NRT or bupropion. CONCLUSION: Further studies are required to address the uncertainty that exists on the most appropriate duration of therapy as well as the effectiveness and safety of combination pharmacotherapy. Post-marketing surveillance continues to play an important role in monitoring the adverse effects events associated with these therapies.

Relaxin family peptides and receptors in mammalian brain.

As a foundation for regulatory and functional studies of central relaxin family peptide receptor systems, we are mapping the distribution of the different receptors in the brain of rat, mouse, and nonhuman primates, attempting to identify the nature of the receptor-positive neurons in key circuits and establish the complementary distribution of the respective ligands in these species. Here we review progress in mapping RXFP1, RXFP2, and RXFP3 (mRNAs and proteins) and their respective ligands and discuss some of the putative functions for these peptides and receptors that are being explored using receptor-selective agonist and antagonist peptides and receptor and peptide gene deletion mouse strains. Comparative studies reveal an association of RXFP1 and RXFP2 with excitatory neurons but a differential regional or cellular distribution, in contrast to the association of RXFP3 with inhibitory neurons. These studies also reveal differences in the distribution of RXFP1 and RXFP2 in rat and mouse brain, whereas the distribution of RXFP3 is more conserved across these species. Enrichment of RXFP1/2/3 in olfactory, cortical, thalamic, limbic, hypothalamic, midbrain, and pontine circuits suggests a diverse range of modulatory actions for these receptors. For example, experimental evidence in the rat reveals that RXFP1 activation in the amygdala inhibits memory consolidation, RXFP2 activation in striatum produces sniffing behavior, and RXFP3 modulation has effects on feeding and metabolism, the activity of the septohippocampal pathway, and spatial memory. Further studies are now required to reveal additional details of these and other functions linked to relaxin family peptide receptor signaling in mammalian brain and the precise mechanisms involved.

Localization of LGR7 gene expression in adult mouse brain using LGR7 knock-out/LacZ knock-in mice: correlation with LGR7 mRNA distribution.

Knowledge of the distribution of the relaxin receptor, LGR7, in the brain provides a basis for studies of the physiologic actions of relaxin. LGR7 knock-out (KO) mice were produced by the in-frame replacement of LGR7 exon 10 and 11 with a LacZ-reporter cassette (knock-in [KI]), and in this study we used LGR7-KO/LacZ-KI mice to determine the regional/cellular distribution of LGR7 gene expression in adult mouse brain by assessing beta-galactosidase activity in perfusion-fixed sections. High densities of beta-galactosidase-positive neurons were detected in anterior olfactory and claustrum/endopiriform nuclei, deep layers of cortex (particularly somatosensory), and the subiculum. Low to moderate densities were detected in olfactory bulb (periglomerular layer), cingulate cortex, subfornical organ, hippocampal CA2/dentate hilus, amygdala, hypothalamus, and thalamus. This LGR7/LacZ expression appears to recapitulate that of native LGR7 in wild-type mice and provides a model to further investigate the phenotype of LGR7-responsive neurons in the brain and to help reveal functions associated with central relaxin signaling.

Effect of p75 neurotrophin receptor antagonist on disease progression in transgenic amyotrophic lateral sclerosis mice.

Neurotrophin level imbalances and altered p75 neurotrophin receptor (p75(NTR)) expression are implicated in spinal motor neuron degeneration in human and mouse models of amyotrophic lateral sclerosis (ALS). Recently, elevated reactive astrocyte-derived nerve growth factor (NGF) was linked to p75(NTR)-expressing motor neuron death in adult transgenic ALS mice. To test the role of NGF-dependent p75(NTR)-mediated signalling in ALS, we examined the effects of a cyclic decapeptide antagonist of p75(NTR) ligand binding by using neurotrophin-stimulated cell death assays and transgenic ALS mice. Murine motor neuron-like (NSC-34) cell cultures expressed full-length and truncated p75(NTR), tyrosine receptor kinase B (TrkB), and the novel neurotrophin receptor homolog-2 (NHR2) but were TrkA deficient. Accordingly, treatment of cells with NGF induced dose-dependent cell death, which was significantly blocked by the cyclic decapeptide p75(NTR) antagonist. Application of brain-derived neurotrophic factor, neurotrophin-3, or neurotrophin-4 to cultures increased cell proliferation, and such trophic effects were abolished by pretreatment with the tyrosine kinase inhibitor K-252a. Systemic administration of a modified cyclic decapeptide p75(NTR) antagonist conjugated to the TAT4 cell permeabilization sequence to presymptomatic transgenic SOD1(G93A) mice affected neither disease onset nor disease progression, as determined by hindlimb locomotor, grip strength, and survival analyses. These studies suggest that disrupting NGF-p75(NTR) interactions by using this approach is insufficient to alter the disease course in transgenic ALS mice. Thus, alternate ligand-independent pathways of p75(NTR) activation or additional NGF receptor targets may contribute to motor neuron degeneration in ALS mice.

Isolation and culture of motor neurons from the newborn mouse spinal cord.

A protocol for the isolation and culture of motor neurons from postnatal day 1 mouse spinal cord is described. After 72 h in culture, phase contrast microscopy reveals healthy cells with motor neuronal morphology and extensive neuritic processes. These neurons express the 75-kDa low-affinity neurotrophin receptor (p75NTR) and choline acetyltransferase (ChAT), both proteins are specifically expressed by neonatal and embryonic motor neurons in vivo. This protocol can be adapted for various postnatal motor neuron assays.