Attention-Deficit/Hyperactivity Disorder-Related Self-Reported Symptoms Are Associated With Elevated Concussion Symptomatology.

The aim of the present investigation was to provide insight into how postconcussion symptomatology may be altered in individuals exhibiting attention-deficit/hyperactivity disorder (ADHD)-related behaviors and examine factors that may be responsible for driving such relationships. A total of 99 individuals were assessed during the subacute phase of concussion recovery. Inattentive symptomatology, but not diagnosis of ADHD, was related to greater concussion-symptom severity and overall symptoms endorsed. Cluster and factor analyses highlighted that the relationship between ADHD symptomatology and concussion symptomatology was not a function of overlapping constructs being assessed (i.e., concussion-related symptomatology was not a proxy of ADHD-related symptomatology). These relationships were not mediated by parental observations of impairments in behaviors associated with executive functioning (i.e., executive dysfunction was not driving the greater concussion-related symptomatology associated with ADHD-related symptomatology). These findings highlight the importance of moving beyond categorical frameworks of ADHD to, instead, consider the continuum of underlying behaviors.

A low cost, safe, disposable, rapid and self-sustainable paper-based platform for diagnostic testing: lab-on-paper.

There is a strong interest in the use of biopolymers in the electronic and biomedical industries, mainly towards low-cost applications. The possibility of developing entirely new kinds of products based on cellulose is of current interest, in order to enhance and to add new functionalities to conventional paper-based products. We present our results towards the development of paper-based microfluidics for molecular diagnostic testing. Paper properties were evaluated and compared to nitrocellulose, the most commonly used material in lateral flow and other rapid tests. Focusing on the use of paper as a substrate for microfluidic applications, through an eco-friendly wax-printing technology, we present three main and distinct colorimetric approaches: (i) enzymatic reactions (glucose detection); (ii) immunoassays (antibodies anti-Leishmania detection); (iii) nucleic acid sequence identification (Mycobacterium tuberculosis complex detection). Colorimetric glucose quantification was achieved through enzymatic reactions performed within specific zones of the paper-based device. The colouration achieved increased with growing glucose concentration and was highly homogeneous, covering all the surface of the paper reaction zones in a 3D sensor format. These devices showed a major advantage when compared to the 2D lateral flow glucose sensors, where some carryover of the coloured products usually occurs. The detection of anti-Leishmania antibodies in canine sera was conceptually achieved using a paper-based 96-well enzyme-linked immunosorbent assay format. However, optimization is still needed for this test, regarding the efficiency of the immobilization of antigens on the cellulose fibres. The detection of Mycobacterium tuberculosis nucleic acids integrated with a non-cross-linking gold nanoprobe detection scheme was also achieved in a wax-printed 384-well paper-based microplate, by the hybridization with a species-specific probe. The obtained results with the above-mentioned proof-of-concept sensors are thus promising towards the future development of simple and cost-effective paper-based diagnostic devices.

Increased anxiety and depression among collegiate athletes with comorbid ADHD and history of concussion.

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is prevalent among student-athletes when compared to the general population. Mental health disruptions (i.e., depression or anxiety) are common among student-athletes, and risk of experiencing depressive and anxious symptoms may be even greater among student-athletes that have incurred concussion. OBJECTIVE: To examine the influence of pre-existing ADHD and history of concussion on mental health in collegiate student-athletes. DESIGN: Retrospective cross-sectional study. SETTING: National Collegiate Athletic Association Division-I (NCAA) athletics. PATIENTS: Between 2010 and 2017, student-athletes at a Southeastern NCAA Division-I institution were surveyed as part of a Performance, Health, and Wellness Program. Analyses were conducted using a sample of 324 student athletes (212 female) with either a prior diagnosis of ADHD, a prior history of a sport-related concussion, both prior diagnosis of ADHD and a history of sport-related concussion, or neither (controls). MAIN OUTCOME MEASURE(S): Symptomatology associated with ADHD was characterized using the Behavior Assessment System for Children Self-Report of Personality College Version. The State-Trait Anxiety Inventory and the Center of Epidemiological Studies-Depression Scale examined anxious and depressive symptomatology. RESULTS: Student-athletes with ADHD and a history of concussion had 16.4 times greater odds of exhibiting clinically significant symptoms of state anxiety and 7.9 times greater odds of exhibiting clinically significant symptoms of depression, relative to control student-athletes. Every participant with both a diagnosis of ADHD and a history of concussion exhibited clinically significant attentional problems. CONCLUSIONS: Having both ADHD and a history of concussion may have a synergistic effect on mental health beyond that of ADHD and/or concussion alone. Additional longitudinal research is necessary to verify current findings. However, athletic trainers and other health care professionals are encouraged to be mindful of student-athletes with ADHD, as they may be more vulnerable to experiencing symptoms of depression and state anxiety with elevated inattentive behaviors following a concussion.

Concussion Exposure and Suicidal Ideation, Planning, and Attempts Among US High School Students.

CONTEXT: Interest is growing in the association between repetitive concussions and mental health. However, studies on the relationship between concussion frequency and adverse mental health outcomes among female and male youth are lacking. OBJECTIVES: To examine the association between self-reported concussion frequency and nonfatal suicidal behaviors among youth and to explore the possible interaction of biological sex. DESIGN: Retrospective cross-sectional survey. SETTING: National Youth Risk Behavior Surveillance System. PATIENTS OR OTHER PARTICIPANTS: United States secondary school students (N = 28 442). MAIN OUTCOME MEASURE(S): Exposure variables were the frequency of self-reported sport- or recreation-related concussion in the previous 12 months (0, 1, ≥2). Outcome variables were feelings of self-reported sadness or hopelessness and suicidal ideation, planning, and attempts. Covariates were age, sex, race and ethnicity, bullying victimization, sexual orientation, and physical activity. RESULTS: Students who reported ≥2 concussions were at significantly greater odds of reporting suicidal attempts (adjusted odds ratio = 2.03; 95% CI = 1.43, 2.88) when compared with students reporting a single concussive event during the past 12 months. However, sex interactions revealed that this finding may have been driven by males; the strength of associations did not increase from single to multiple concussions among females. CONCLUSIONS: Our findings suggest that adolescents who reported concussion were at increased odds of reporting poor mental health and suicidal behaviors. Moreover, an increased number of concussive events may be associated with significantly greater odds of reporting suicidal attempts, particularly among males. Irrespective of sex, health care professionals should closely monitor mental health behaviors in adolescents with repetitive concussions, especially those that occur in close temporal proximity.

Hormonal Contraceptives Do Not Influence Concussion Recovery in Collegiate Athletes: Data from the NCAA-DoD CARE Consortium.

INTRODUCTION: The hormonal withdrawal hypothesis suggests that progesterone reduction in women after concussion may lead to greater symptom burden and longer recoveries. Current evidence indicates that hormonal stability after head injury may be an important moderator of postconcussive recovery. Thus, female athletes using hormonal contraceptives (HC) may exhibit better recovery profiles as their hormone levels are artificially stabilized. Our investigation sought to examine the relation between HC use and concussion outcomes in female student-athletes. METHODS: This longitudinal study examined concussion outcomes from female student-athletes participating in the NCAA-DoD CARE Consortium Research Initiative, including academic years 2014 to 2020. Eighty-six female collegiate athletes reporting HC use (HC+) were group matched on age, body mass index, race/ethnicity, sport contact level, concussion history, and current injury characteristics (i.e., amnesia, loss of consciousness) to 86 female collegiate athletes reporting no HC use (HC-). All participants had sustained a concussion and completed the Sport Concussion Assessment Tool, 3rd edition Symptom Scale, Brief Symptom Inventory-18, and Immediate Post-concussion Assessment and Cognitive Testing at preinjury baseline, 24 to 48 h postinjury, and when cleared for unrestricted return to play. To provide an index of recovery trajectory, days between injury and unrestricted return to play were calculated. RESULTS: Groups did not differ on length of recovery, postconcussion symptoms, psychological health, or cognitive assessments. No differences were observed between groups on any measure when accounting for baseline levels of performance. CONCLUSIONS: Our findings suggest that HC use does not influence recovery trajectory, symptoms, or recovery of cognitive function after concussion.

Halide Salt-Catalyzed Crosslinked Polyurethanes for Supercapacitor Gel Electrolyte Applications.

Gel polymer electrolytes are an important advancement in energy storage technology due to their enhanced safety and practical ionic conductivities at ambient temperatures. Herein, a simple one-step facile synthesis of chemically crosslinked polyurethanes containing polyethylene oxide (PEO) and polypropylene oxide (PPO) macromolecular segments was developed, using ubiquitous non-toxic tetrabutylammonium or potassium chloride and bromide salts as catalysts. These salts were shown to catalyze the gelation of diol-diisocyanate polyaddition reactions within minutes. When impregnated with a liquid electrolyte, the resulting gel electrolyte exhibited a practical ionic conductivity of 1.1×10-4  S cm-1 at 40 °C and low segmental chain motion activation energy (11 kJ mol-1 ). These findings further promote PEO-PPO polyurethanes as a biocompatible class of materials suitable for further exploration as gel polymer electrolytes for supercapacitors.

The Influence of Family History of Neurodegenerative Disease on Adolescent Concussion Outcomes.

Evidence suggests that factors associated with a family history of neurodegenerative disease (fhNDD) may influence outcomes following a concussion. However, the relevance of these findings in adolescent populations has not been fully explored. Therefore, the present study sought to evaluate the relationship between fhNDD and neurological outcomes following an adolescent concussion. Data from a local pediatric concussion clinic were used to compare adolescents with (n = 22) and without (n = 44) an fhNDD. Clinical symptom burden, emotional health, cardio-autonomic function, and cognitive performance were assessed at initial (~2 weeks) and follow-up (~5 weeks) post-injury evaluations. Cardio-autonomic function was assessed at rest and during isometric handgrip contraction (IHGC). Results indicated no significant group differences in emotional health or cognitive performance. Across evaluations, those with an fhNDD exhibited greater somatic symptom severity, alterations in HRV at rest, and early blunted cardio-autonomic reactivity during IHGC compared to those without an fhNDD. These findings suggest that positive fhNDD is negatively associated with clinical symptomology and cardio-autonomic functioning following an adolescent concussion. Further, these findings encourage clinicians to utilize a comprehensive neurological evaluation to monitor concussion recovery. Future studies should look into exploring the role of specific neurodegenerative processes and conditions on concussion outcomes in adolescents.

Predictive Value of Subacute Heart Rate Variability for Determining Outcome Following Adolescent Concussion.

Objective assessments of concussion recovery are crucial for facilitating effective clinical management. However, predictive tools for determining adolescent concussion outcomes are currently limited. Research suggests that heart rate variability (HRV) represents an indirect and objective marker of central and peripheral nervous system integration. Therefore, it may effectively identify underlying deficits and reliably predict the symptomology following concussion. Thus, the present study sought to evaluate the relationship between HRV and adolescent concussion outcomes. Furthermore, we sought to examine its predictive value for assessing outcomes. Fifty-five concussed adolescents (12-17 years old) recruited from a local sports medicine clinic were assessed during the initial subacute evaluation (within 15 days postinjury) and instructed to follow up for a post-acute evaluation. Self-reported clinical and depressive symptoms, neurobehavioral function, and cognitive performance were collected at each timepoint. Short-term HRV metrics via photoplethysmography were obtained under resting conditions and physiological stress. Regression analyses demonstrated significant associations between HRV metrics, clinical symptoms, neurobehavioral function, and cognitive performance at the subacute evaluation. Importantly, the analyses illustrated that subacute HRV metrics significantly predicted diminished post-acute neurobehavioral function and cognitive performance. These findings indicate that subacute HRV metrics may serve as a viable predictive biomarker for identifying underlying neurological dysfunction following concussion and predict late cognitive outcomes.

Wheel running for 26 weeks is associated with sustained vascular plasticity in the rat motor cortex.

Vascular pathologies represent the leading causes of mortality worldwide. The nervous system has evolved mechanisms to compensate for the cerebral hypoxia caused by many of these conditions. Vessel dilation and growth of new vessels are two prominent responses to hypoxia, both of which play a critical role in maintaining cerebral homeostasis. One way to facilitate cerebrovascular plasticity, and develop neuroprotection against vascular pathologies, is through aerobic exercise. The present study explored the long-term consequences of aerobic exercise on vascular structure and function in the motor cortex. Rats were assigned to a sedentary condition or were provided access to running wheels for 26 weeks. Rats were then anesthetized, and angiograms were captured using spectral domain optical coherence tomography (SD-OCT) to explore cerebrovascular reactivity in response to altered oxygen and carbon dioxide status. Following this procedure, all rats were euthanized, and unbiased stereological quantification of blood vessel density was collected from sections of the primary motor cortex infused with India ink. Results demonstrated that chronic exercise increased capillary and arteriole surface area densities and enhanced arteriole reactivity in response to hypercapnia-hypoxia, as displayed by increased vasodilation within the motor cortex of exercised animals.

Spin trapping agent phenyl N-tert-butylnitrone protects against the onset of drug-induced insulin-dependent diabetes mellitus.

Insulin-dependent diabetes mellitus is an autoimmune disease believed to be caused by an inflammatory process in the pancreas leading to selective destruction of the beta-cells. Cytokines and nitric oxide (NO) have been shown to be involved in this destruction. Phenyl N-tert-butylnitrone (PBN) has demonstrated protective effects against several pathological conditions including ischemia-reperfusion injury and endotoxin-induced shock. We report here that PBN co-administration can prevent the onset of the STZ-induced diabetes in mice. PBN co-treatment inhibited the streptozotocin (STZ)-induced hyperglycemia, the elevation in the level of glycated hemoglobin and weight loss in the treated mice. Histological observations indicated destruction of B-cells in the STZ-treated animals and its prevention by PBN co-treatment. EPR spin trapping experiments in the pancreas indicated the in vivo formation of NO in STZ-treated animals and its attenuation by PBN treatment.

Conditioning nerve crush accelerates cytoskeletal protein transport in sprouts that form after a subsequent crush.

To examine the relationship between axonal outgrowth and the delivery of cytoskeletal proteins to the growing axon tip, outgrowth was accelerated by using a conditioning nerve crush. Because slow component b (SCb) of axonal transport is the most rapid vehicle for carrying cytoskeletal proteins to the axon tip, the rate of SCb was measured in conditioned vs. sham-conditioned sprouts. In young Sprague-Dawley rats, the conditioning crush was made to sciatic nerve branches at the knee; 14 days later, the test crush was made where the L4 and L5 spinal nerves join to form the sciatic nerve in the flank. Newly synthesized proteins were labeled in motor neurons by injecting 35S-methionine into the lumbar spinal cord 7 days before the test crush. The wave of pulse-labeled SCb proteins reached the crush by the time it was made and subsequently entered sprouts. The nerve was removed and sectioned for SDS-PAGE and fluorography 4-12 days after the crush. Tubulins, neurofilament proteins, and representative "cytomatrix" proteins (actin, calmodulin, and putative microtubule-associated proteins) were removed from gels for liquid scintillation counting. Labeled SCb proteins entered sprouts without first accumulating in parent axon stumps, presumably because sprouts begin to grow within hours after axotomy. The peak of SCb moved 11% faster in conditioned than in sham-conditioned sprouts: 3.0 vs. 2.7 mm/d (p less than 0.05). To confirm that sprouts elongate more rapidly when a test crush is preceded by a conditioning crush, outgrowth distances were measured in a separate group of rats by labeling fast axonal transport with 3H-proline 24 hours before nerve retrieval.(ABSTRACT TRUNCATED AT 250 WORDS)

Lumbar motor neuron size and number is affected by age in male F344 rats.

Motor neurons in the spinal cord of old rats appear similar in size but less numerous compared with those in mature rats; they also contain a large amount of lipofuscin, the lipid peroxidation by-product whose function is largely unknown. The object of this study was to morphometrically characterize motor neurons found in the L4/L5 lumbar spinal cord of mature (6-month) and old (22-month) rats. Paraformaldehyde-fixed, lumbar spinal cords from six rats at each age were embedded in paraffin, sectioned at 6 microm and stained with 0.1% toluidine blue. The nucleolar diameter and area from a minimum of 34 motor neurons per spinal cord were measured. Motor neuron number was calculated using Abercrombie's (Abercrombie, 1946) formula after correcting for tissue shrinkage. Motor neuron number was decreased with age while the neuronal area increased with age. Nucleolar diameter also increased in old rats. Frequency distributions of motor neuron area revealed unimodal distributions of motor neurons rats of both ages. We suggest that larger nucleolar diameter reflects more metabolically active neurons in old rats while larger neuron area is a reflection of the presence of lipofuscin in old motor neurons.

The effect of age and injury on the expression of inducible nitric oxide synthase in facial motor neurons in F344 rats.

Nitric oxide has been implicated in both normal neuronal aging as well as nerve repair events because of its known roles in synaptic plasticity, synaptogenesis and neuroplathologic processes. In this study, we have determined the effect of aging, by comparing brainstem facial motor neurons (FMNs) as well as blood vessels, from adult F344 rats to those in old animals. Inducible nitric oxide synthase (iNOS) expression was determined both by immunohistochemistry using an antibody to iNOS on tissue sections and slot blots. In adult rats, iNOS expression was detectable only in FMNs and not in blood vessels. In old rats, there were robust levels of iNOS protein in blood vessels, while iNOS protein was not detectable in FMNs from old rats. There was also a 12-fold increase in iNOS expression in isolated blood vessels from old rats compared to vessels from adult animals. To determine the effect of injury on iNOS expression, the facial nerve was transected and immunocytochemistry performed as above. After nerve transection in adult rats, iNOS was demonstrable only in blood vessels after 1 day, but by 7 days iNOS protein immunoreactivity was robust in FMNs. In old animals, iNOS protein expression was observed only in FMNs at 1 day, but by 7 days after injury, protein immunoreactivity was localized to the blood vessels. These data suggest that aging and injury differentially affect the expression of iNOS and that the up-regulation of iNOS may be important for the availability of nitric oxide in the aged or injured nervous system.

Fast axonal transport rates are unchanged in 6- and 24-month F344 rats.

The maximum rate of fast axonal transport in motor axons at 6 and 24 months was measured in F344 rats. Tritiated proline was injected near sciatic motoneurons and rats were killed after 2-5 h. Nerves were processed for liquid scintillation spectroscopy and fast transport rates calculated. The rates, in 6- and 24-month rats, were 373 +/- 12 mm/day and 368 +/- 10 mm/day, respectively. Thus, the maximum fast transport rate is unchanged with age in F344 rats.

Direct measurement of fast axonal transport rates in corticospinal axons of the adult rat.

The bi-directional movement of proteins from the soma to the axon terminal is called axonal transport. Fast anterograde transport moves organelles and membrane-bound proteins distally. Fast transport rates were measured in corticospinal tract axons of male Sprague-Dawley rats by microinjection of tritiated proline into the sensorimotor cortex. Animals were killed after 3-5 h and the tract cut into 1 mm segments. A bimodal wave of radiolabeled proteins was evident, with the first peak at the spino-medullary junction and the second peak in cervical spinal segments. The fast transport rate was calculated at the leading edge of the distal wave, and found to be 303 +/- 44 mm/day.

Examining cerebral angiogenesis in response to physical exercise.

Capillary growth and expansion (angiogenesis) is a prerequisite for many forms of neural and behavioral plasticity. It is commonly observed in both brain and muscle of aerobically exercising animals. As such, several histological methods have been used to quantify capillary density, including perfusion with India ink, various Nissl stains, and immunohistochemistry. In this chapter, we will describe these histological procedures and describe the stereological analysis used to quantify vessel growth in response to aerobic exercise.

Changing practice on confidentiality: a cause for concern. Commentary 1: Confidentiality: the dangers of anything weaker than the medical ethic.

KIE: Articles by D.J. Kenny and Derek F.H. Pheby in the same issue of the Journal of Medical Ethics suggested that expanded legal rights are needed in Great Britain to safeguard medical confidentiality and to reinforce the "ethics of virtue" of the medical profession. The author of this commentary contends that a legal rights approach would subject medical practice to greater regulation and prove less powerful than the current peer review mechanism in protecting ethical standards of confidentiality.^ieng

Differential effects of age on neuromuscular transmission in partially denervated mouse muscle.

The response of the neuromuscular junction to expansion of the motor unit after partial denervation (section of L5 root) was compared in soleus muscles from young (5-8 month) and old (25-30 month) mice. The object was to determine the relative capacity of young and old motor neurons to adapt to an enlarged functional field of innervation, and to delineate physiological parameters that are compromised under these conditions. Neuromuscular function was studied at 30, 60, and 120 d after partial denervation. The initial (18-23) and postoperative number (5-8) of motor units was the same in both age groups. Twitch strength declined in proportion to loss of motor units at 30 d but returned completely (young) or nearly completely (old) by 60 d. In old but not young muscle, the safety factor (assayed by twitch depression in low calcium) was decreased even before functional sprouting had occurred, indicating a reduced safety factor in nondenervated junctions. The proportion of fibers with "long" latencies (delay between stimulation and endplate potential) increased transiently (at 30 d) in young muscle but persisted without recovery at 120 d in regenerated junctions in old muscle. After partial denervation, decline in miniature endplate potential (mepp) amplitude, in mepp frequency, and in estimated quantal content of evoked release was relatively more pronounced in old than in young mice, and in the case of mepp amplitude and frequency, more persistent. Mepp amplitude was also decreased in presumed nondenervated junctions of old muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Assembly of microfilaments and microtubules from axonally transported actin and tubulin after axotomy.

The slow component (SC) of axonal transport conveys structural proteins, regulatory proteins, and glycolytic enzymes toward the axon tip at 1-6 mm/day. Following axon interruption (axotomy), the rate of outgrowth corresponds to the rate of SCb-the fastest subcomponent of SC. Both axonal outgrowth and SCb accelerate 20-25% after axotomy. Tubulin and actin are the major proteins being carried by SCb. To further characterize the acceleration of SCb, we measured the equilibrium between subunits and polymers for both actin and tubulin. We radiolabeled newly synthesized proteins in rat motor neurons by microinjecting [35S]methionine into the spinal cord 7 days after crushing the sciatic nerve (85 mm from the spinal cord). Nerves were removed 7 days later for homogenization in polymer-stabilizing buffer (PSB) and centrifugation, followed by SDS-PAGE of supernatants (S) and pellets (P). We removed beta-tubulin, actin, and the medium-weight neurofilament protein (NF-M) from each gel by using the fluorogram as a template. After solubilizing gel segments for liquid scintillation spectrometry, we expressed counts as a polymerization ratio: P/[S+P]. In the nerve segments that contained radiolabeled Scb proteins, located 24-36 mm from the spinal cord, axotomy increased the polymerization ratio of SCb actin from 0.23 to 0.36 (P < 0.05) but had no effect on SCb beta-tubulin. In a separate experiment, we added 12 microM taxol to PSB to stabilize newly assembled microtubules. Adding taxol did not alter the polymerization ratio for SCb beta-tubulin in sham-axotomized nerves but aid increase the ratio in axotomized nerves, from 0.44 to 0.63 (P < 0.05); polymerization ratios for SCb actin were unaffected. We conclude that the assembly of microfilaments and microtubules increases to provide cytoskeletal elements for axon sprouts. The resulting loss of actin and tubulin subunits may play a role in the acceleration of SCb.

Age differences in morphology of reinnervation of partially denervated mouse muscle.

The effect of age on the ability of motor neurons to develop and maintain an enlarged total axonal and synaptic volume was compared in soleus muscles of 5-8-month and 25-30-month mice, 30-120 d after partial denervation. Before and after partial denervation (transection of the L5 root), the total number of muscle fibers was the same in all muscles. However, in young animals, there was only some transient atrophy and hypertrophy mostly receded by 120 d, whereas in old muscle, a more prominent early atrophy was followed by persistent hypertrophy. Ectopic endplates were not found. In zinc-iodide-osmium (ZIO) stained preparations, muscle fibers with small nerve terminals were present at 60 d and were still present in old muscle at 120 d. Fluorescent staining of nerve terminals and acetylcholine receptors revealed that in young muscle, postsynaptic sites were nearly or completely reoccupied by 60 d. In old muscle, about 22% of former junctions were denervated, with the remainder minimally to fully reinnervated. At 60 d and thereafter, collateral sprouts originated from nodes of Ranvier in both young and old muscle and were remyelinated in young but mainly unmyelinated and remarkably tortuous in old animals. These results, confirmed with immunofluorescent strains for myelin basic protein and neurofilaments, account for many of the physiological findings (Jacob and Robbins, 1990). Motor unit size expanded 2.5 times in young and 2 times in old muscle at 60 d after partial denervation. However, the increment in total quantal output and nerve terminal volume per motor neuron was 60-100% greater than control in young but only 20-25% greater in old muscle, with little further recovery. This inability of the motor neuron in old mice to expand the field of innervation may reflect a limitation imposed by reduced axonal transport. The present findings may elucidate the muscle weakness in postpolio syndrome and amyotrophic lateral sclerosis.