Chronic Deficits Research Articles

Acute and Reversible Hypothalamic Symptoms in a Lateral Head Impact Mouse Model of Mild Traumatic Brain Injury.

Central autonomic and endocrine dysfunctions following traumatic brain injury (TBI) are believed to involve the hypothalamus; however, underlying mechanisms are unknown. Although chronic deficits might be caused by irreversible tissue damage, various neuroendocrine and autonomic symptoms are only observed transiently, suggesting they might result from a temporary alteration in the activity of hypothalamic neurons. We therefore examined if a mouse model of mild TBI could induce reversible autonomic phenotypes and cause acute changes in c-Fos expression within corresponding regions of the hypothalamus. Adult C57Bl/6 male mice were lightly anesthetized with isoflurane and subjected to TBI by lateral head impact using a Gothenburg impactor. Mice treated the same way, but without the head impact served as controls (shams). We monitored body weight and core body temperature by infrared thermography and performed immunohistochemistry against c-Fos in various regions of the hypothalamus. We determined that a projectile velocity of 9 m/s significantly delayed recovery from the anesthesia without inducing skull fractures and signs of discomfort disappeared within 3 h, as assessed by grimace scale. Compared with shams, TBI mice displayed a rapid decrease in core body temperature which resolved within 48 h. Daily body weight gain was also significantly lower in TBI mice on the day following injury but recovered thereafter. c-Fos analysis revealed a significantly higher density of c-Fos-positive cells in the paraventricular nucleus and a significantly lower density in the median preoptic nucleus and medial preoptic area. We conclude that mild TBI induced by a single lateral head impact in mice at 9 m/s produces acute and reversible symptoms associated with hypothalamic dysfunction accompanied by significant changes in c-Fos expression within relevant areas of the hypothalamus. These findings support the hypothesis that a temporary alteration of neuronal activity may underlie the expression of reversible central autonomic and neuroendocrine symptoms.

Post-stroke aphasia rehabilitation using an adapted visual P300 brain-computer interface training: improvement over time, but specificity remains undetermined.

This study aimed to evaluate the efficacy of visual P300 brain-computer interface use to support rehabilitation of chronic language production deficits commonly experienced by individuals with a left-sided stroke resulting in post-stroke aphasia. The study involved twelve participants, but five dropped out. Additionally, data points were missing for three participants in the remaining sample of seven participants. The participants underwent four assessments-a baseline, pre-assessment, post-assessment, and follow-up assessment. Between the pre-and post-assessment, the participants underwent at least 14 sessions of visual spelling using a brain-computer interface. The study aimed to investigate the impact of this intervention on attention, language production, and language comprehension and to determine whether there were any potential effects on quality of life and well-being. None of the participants showed a consistent improvement in attention. All participants showed an improvement in spontaneous speech production, and three participants experienced a reduction in aphasia severity. We found an improvement in subjective quality of life and daily functioning. However, we cannot rule out the possibility of unspecific effects causing or at least contributing to these results. Due to challenges in assessing the patient population, resulting in a small sample size and missing data points, the results of using visual P300 brain-computer interfaces for chronic post-stroke aphasia rehabilitation are preliminary. Thus, we cannot decisively judge the potential of this approach.

SOIL FERTILITY AND HYDROGEOLOGICAL CONDITIONS OF THE PILOT PLOT LOCATED ON THE TERRITORY OF THE MODULAR BIOLOGICAL TREATMENT PLANT OF THE VILLAGE OF TASBOGET

Forecast calculations show that the possible use of surface runoff for agriculture and industrial production by 2040 will be no more than 24.4 km3/year, and taking into account non-productive losses it will be possible to use up to 21.5 km3/year of water resources [1]. On the territory of Kyzylorda province, the water factor acquires a leading role in the ecological sustainability of the natural environment. The main cause of environmental problems in the river basin is pollution and chronic water deficit. Therefore, providing the population and various sectors of the national economy with water in the required quantity and quality is the most important problem of our time. The level of anthropogenic pressures on water resources is determined by quantitative and qualitative indicators of water use, wastes of life activity entering the water source and their compatibility with the natural environment. Despite the reduction of return water discharges to water sources, water quality in all water bodies remains unsatisfactory [2]. At the present stage, both in Kazakhstan and abroad, to utilize the increasing volume of wastewater, the natural method of water treatment on irrigated fields has been increasingly used, with maximum use of nutrients contained in wastewater. In this case, irrigated fields can be considered as the final link of their natural disinfection treatment, which has socio-economic, environmental and technological aspects.

Бюджетная политика развитых стран: игра по правилам?

The article examines the reasons for the adoption of fiscal rules in advanced economies, their main types, evolution and results of application. In the practice of fiscal policy over the past decades, there has been a steady trend towards budget deficits. There are two main reasons that explain this widespread deficit bias phenomenon: the tendency to push out the financial discipline burden to future governments or even to future generations and the interplay of political processes and interest group activities (common pool effect). Chronic budget deficits and growing public debts have prompted many countries to adopt certain national and supranational (in the EU) fiscal rules – long-lasting constraints on fiscal policy through numerical limits on main budgetary aggregates: budget balance, debt, expenditure or revenue. Fiscal rules can promote financial discipline and reduce the deficit bias in several ways. This influence on fiscal behavior arises from their capacity to “tie the hands” of policymakers and to be a useful signaling tool, helping to reduce the asymmetry of information between policymakers and voters. But the compliance track record with fiscal rules is relatively poor. They have failed to provide sufficient fiscal discipline: the deficit bias persists and the debt-to-GDP ratio in most advanced economies continues to grow. The adopted budget rules are periodically suspended, they are subject to revision, sometimes formally implemented by applying the creative accounting, policymakers use them as a tool of political bargaining. Ultimately, fiscal discipline does not depend on the existence of rules, but on the willingness of politicians to comply with this discipline.

The emerging roles and therapeutic implications of immunosenescence-mediated inflammaging in age-related hearing loss.

Age-related hearing loss (ARHL) represents one of the most prevalent chronic sensory deficits experienced by the elderly, significantly diminishing their quality of life and correlating with various medical and psychological morbidities. This condition arises from the cumulative effects of aging on the auditory system, implicating intricate interactions between genetic predispositions and environmental factors. Aging entails a progressive decline in immune system functionality, termed immunosenescence, leading to a chronic low-grade inflammation known as inflammaging. This phenomenon potentially serves as a common mechanism underlying ARHL and other age-related pathologies. Recent research suggests that rejuvenating immunosenescence could mitigate inflammaging and ameliorate age-related functional declines, offering promising insights into anti-aging therapies. Consequently, this review endeavors to elucidate the role of immunosenescence-mediated inflammaging in ARHL progression and discuss its therapeutic implications.

A Giant Frontoethmoidal Sinus Osteoma Presenting With Frequent Sleep Apnea Attacks: A Case Report

Background: Paranasal sinus osteomas are benign, slow-growing tumors that are typically asymptomatic. However, in rare cases, these tumors can grow to a giant size and extend into neighboring structures such as the brain, orbit, or nasal cavity, leading to clinical symptoms. These symptoms may include chronic headaches, rhinorrhea, neurological deficits, and visual impairment. Case presentation: Here, we present the case of a 27-year-old male patient who presented to our hospital with chronic headaches and frequent sleep apnea. Upon rhinoscopic examination, mucosal polyposis was observed. Further evaluation through computed tomography revealed a giant fibroosseous tumor in the frontal sinus, which exhibited aggressive extension into the brain parenchyma. Contrast-enhanced magnetic resonance imaging confirmed the presence of a giant tumor with an 8 cm diameter, exerting a mass effect on the underlying brain tissue. To address this complex case, the patient underwent a combined transcranial and transnasal surgical approach. Following the surgery, the patient experienced significant improvement in his symptoms. Conclusions: This report highlights a rare case of sleep apnea secondary to a giant frontoethmoidal osteoma with intracranial extension. The presence of frontal sinus osteomas can lead to serious clinical consequences. Timely diagnosis and intervention are crucial to prevent intracranial extension and mitigate potential complications associated with these lesions.

Optimizing Surgical Strategy for Cervical Spinal Deformity: Global Alignment and Surgical Targets.

Cervical spinal deformity (CSD) is a complex condition characterized by abnormal curvature and cervical spine alignment. It can lead to a multitude of symptoms, including chronic pain, neurological deficits, and functional impairments, severely impacting an individual's health-related quality of life (HRQoL). Surgical intervention is often necessary to address the deformity and alleviate symptoms, but optimal surgical strategies remain a topic of ongoing research and debate. This narrative review aims to provide an in-depth overview of the surgical management of CSD, focusing on optimizing patient outcomes and enhancing readers' understanding of the complexities involved. We begin by discussing the importance of preoperative assessment, including comprehensive radiographic evaluation and careful consideration of the global spinal alignment. The relationship between the cervical spine and the reciprocal changes that occur are explored to guide surgeons in their decision-making process. Furthermore, we delve into the selection of fusion levels, emphasizing the significance of identifying the primary driver of deformity. We review the current literature on optimal alignment targets and strategies to optimize surgical planning. By providing a comprehensive analysis of the surgical management of CSD, this review aims to enhance the readers' knowledge and assist surgeons in making informed decisions when planning and executing surgical interventions. Understanding the intricacies of CSD correction and the latest advancements in the field can ultimately improve patient outcomes and enhance HRQoL for individuals suffering from this challenging condition.

Effects of the China-Pakistan Economic Corridor (CPEC) on the Economies of China and Pakistan

China-Pakistan Economic Corridor (CPEC), which is an infrastructure and economic development project initiated by China in Pakistan in 2013. The project aims to connect China's western province of Xinjiang to the Pakistani port of Gwadar through a network of roads, railways, pipelines, and power plants. The CPEC is expected to bring several benefits to both China and Pakistan, including expanding China's economic and geopolitical influence in the region and addressing Pakistan's chronic infrastructure deficits, creating new jobs, and attracting foreign investment. The CPEC can also help to alleviate China's domestic overcapacity issues and reduce its dependence on the South China Sea for its energy imports. Moreover, it can improve Pakistan's regional and global connectivity and enhance its geopolitical importance as a gateway to South Asia and the Middle East. However, the success of the CPEC will depend on various factors, including political stability, security, and effective implementation of the project. Overall, the CPEC represents a win-win scenario for China and Pakistan, as it can provide economic benefits to both countries while promoting regional connectivity and integration.

Epidemiology of sleep patterns and circadian typology in uruguayan children: The contribution of school shifts

Healthy sleep is defined by the combination of adequate duration, good quality, and regular timing. In children, sleep thus depends on the interplay of individual, parental, organizational, community, and social variables, but only a few studies have addressed this issue in a comprehensive way nationwide. Using the Uruguayan nationally representative survey (Nutrition, Child Development, and Health Survey, Encuesta de Nutrición, Desarrollo Infantil y Salud, ENDIS), we present the first epidemiological characterization of chronobiological and sleep parameters in Latin American children. On average, Uruguayan urban children (n = 2437; 5−10-years old) showed quite late chronotypes (MSFsc = 03:53 ± 1:07), moderate misalignment (SJL = 1.0 ± 0.9 h), and adequate sleep duration (SDweek = 9.9 ± 1.0 h). Further, we show the substantial influence of school shift schedules on children's circadian typology and sleep patterns. Our results show that children attending the morning school shift have a higher risk of sleep problems than afternoon-school shift ones. The chronotype and sleep were earlier in morning-school shift children than in children attending the afternoon school shift. However, morning-school shift children had stronger misalignment, shorter sleep on school days, and a higher risk of chronic sleep deficit and non-healthy circadian misalignment (even worse in late chronotypes) than afternoon-shift children. This evidence points to the need of evaluating policies to reorganize school start times to prevent the negative effects that early schooling seems to have on children's sleep health, which has been neglected so far.

IMPROVING REHABILITATION OUTCOMES FOR PEOPLE AGING WITH LONG-TERM HAND IMPAIRMENTS

Abstract Despite the importance of hand and upper extremity function in ADL performance and successful aging-in-place, contextual and engaging in-home rehabilitation interventions that promote use, feedback of progress, and long-term monitoring of changes in functional ability among individuals with chronic upper limb deficits are lacking. This presentation will present the findings from three TechSAge pilot projects focused on the use of technology to support in-home rehabilitation for individuals aging with long-term upper extremity disabilities. DigiHand, is a smartphone-based application combined with sensor-embedded objects used in daily activities (e.g., coffee cup) that enables users to self-manage their own rehabilitation, obtain feedback on progress to refine movements, and allow remote monitoring by therapists. Similarly, KeyStroke is an in-home piano training mobile app that provides engaging music exercises to promote long-term rehabilitation and therapists’ monitoring of progress of stroke survivors. Finally, 3DP for AT is generating design requirements to support the development of an open-source software tool that would allow assistive technology service providers, who are novice users of 3D printers, to create and fabricate highly customized 3D-printed assistive devices that are more durable, aesthetic, and will better meet the unique needs of people aging with long-term hand impairments.

Spinal Neuronal miR-124 Inhibits Microglial Activation and Contributes to Preventive Effect of Electroacupuncture on Chemotherapy-Induced Peripheral Neuropathy in Mice.

Chemotherapy-induced peripheral neuropathy (CIPN) is a persistent and irreversible side effect of antineoplastic agents. Patients with CIPN usually show chronic pain and sensory deficits with glove-and-stocking distribution. However, whether spinal neuronal microRNA (miR)-124 is involved in cisplatin-induced peripheral neuropathy remains to be studied. In this study, miR-124 was significantly reduced in the spinal dorsal horn in CIPN mice. Overexpression of neuronal miR-124 induced by injecting adeno-associated virus with neuron-specific promoter into the spinal cord of mice prevented the development of mechanical allodynia, sensory deficits, and the loss of intraepidermal nerve fibers induced by cisplatin. Meanwhile, cisplatin-induced M1 microglia activation and the release of proinflammatory cytokines were significantly inhibited by overexpression of neuronal miR-124. Furthermore, electroacupuncture (EA) treatment upregulated miR-124 expression in the spinal dorsal horn of CIPN mice. Interestingly, downregulation of spinal neuronal miR-124 significantly inhibited the regulatory effect of EA on CIPN and microglia activity as well as spinal neuroinflammation induced by cisplatin. These results demonstrate that spinal neuronal miR-124 is involved in the prevention and treatment of EA on cisplatin-induced peripheral neuropathy in mice. Our findings suggest that spinal neuronal miR-124 might be a potential target for EA effect, and we provide, to our knowledge, a new experimental basis for EA prevention of CIPN.

The Drosophila NPY-like system protects against chronic stress-induced learning deficit by preventing the disruption of autophagic flux.

Chronic stress may induce learning and memory deficits that are associated with a depression-like state in Drosophila melanogaster. The molecular and neural mechanisms underlying the etiology of chronic stress-induced learning deficit (CSLD) remain elusive. Here, we show that the autophagy-lysosomal pathway, a conserved cellular signaling mechanism, is associated with chronic stress in Drosophila, as indicated by time-series transcriptome profiling. Our findings demonstrate that chronic stress induces the disruption of autophagic flux, and chronic disruption of autophagic flux could lead to a learning deficit. Remarkably, preventing the disruption of autophagic flux by up-regulating the basal autophagy level is sufficient to protect against CSLD. Consistent with the essential role of the dopaminergic system in modulating susceptibility to CSLD, dopamine neuronal activity is also indispensable for chronic stress to induce the disruption of autophagic flux. By screening knockout mutants, we found that neuropeptide F, the Drosophila homolog of neuropeptide Y, is necessary for normal autophagic flux and promotes resilience to CSLD. Moreover, neuropeptide F signaling during chronic stress treatment promotes resilience to CSLD by preventing the disruption of autophagic flux. Importantly, neuropeptide F receptor activity in dopamine neurons also promotes resilience to CSLD. Together, our data elucidate a mechanism by which stress-induced excessive dopaminergic activity precipitates the disruption of autophagic flux, and chronic disruption of autophagic flux leads to CSLD, while inhibitory neuropeptide F signaling to dopamine neurons promotes resilience to CSLD by preventing the disruption of autophagic flux.

Caffeine Administration Mitigates Chronic Stress-Induced Behavioral Deficits, Neurochemical Alterations, and Glial Disruptions in Rats.

Prolonged exposure to stress has detrimental effects on health, and the consumption of caffeine, mostly contained in energy drinks, has become a widely adopted stress coping strategy. Currently, there is limited information regarding the effects of caffeine intake on chronic stress exposure. Thus, this study investigated the effects of caffeine administration on chronic stress-induced behavioral deficits, neurochemical alterations, and glial disruptions in experimental rats. Thirty male Wistar rats were randomly assigned to five groups (n = 6): non-stress control, stress control, and caffeine groups of doses 12.5, 25, and 50 mg/kg. The stress control and caffeine groups were subjected to an unpredictable chronic mild stress (UCMS) protocol daily for 14 days. The rats were evaluated for phenotypic and neurobehavioral assessments. Thereafter, the rat brains were processed for biochemical and immunohistochemical assays. Caffeine administration was found to ameliorate behavioral dysfunctions in rats exposed to UCMS. The UCMS-induced changes in brain levels of monoamines, cholinesterases, and some oxidative stress biomarkers were reversed by caffeine. Caffeine administration also produced mild protective effects against UCMS-induced changes in GFAP and Iba-1 expression in stress-specific brain regions. These results showed that low and moderate doses of caffeine reversed most of the stress-induced changes, suggesting its ameliorative potential against chronic stress-induced alterations.

Protection of p-Coumaric acid against chronic stress-induced neurobehavioral deficits in mice via activating the PKA-CREB-BDNF pathway

There is a body of evidence to suggest that chronic stress modulates neurochemical homeostasis, alters neuronal structure, inhibits neurogenesis and contributes to development of mental disorders. Chronic stress-associated mental disorders present common symptoms of cognitive impairment and depression with complex disease mechanisms. P-coumaric acid (p-CA), a natural phenolic compound, is widely distributed in vegetables, cereals and fruits. p-CA exhibits a wide range of health-related effects, including anti-oxidative-stress, anti-mutagenesis, anti-inflammation and anti-cancer activities. The current study aims to evaluate the therapeutic potential of p-CA against stress-associated mental disorders. We assessed the effect of p-CA on cognitive deficits and depression-like behavior in mice exposed to chronic restraint stress (CRS); we used network pharmacology, biochemical and molecular biological approaches to elucidate the underlying molecular mechanisms. CRS exposure caused memory impairments and depression-like behavior in mice; p-CA administration attenuated these CRS-induced memory deficits and depression-like behavior. Network pharmacology analysis demonstrated that p-CA was possibly involved in multiple targets and a variety of signaling pathways. Among them, the protein kinase A (PKA) - cAMP-response element binding protein (CREB) - brain derived neurotrophic factor (BDNF) signaling pathway was predominant and further characterized. The levels of PKA, phosphorylated CREB (pCREB) and BDNF were significantly lowered in the hippocampus of CRS mice, suggesting disruption of the PKA-CREB-BDNF signaling pathway; p-CA treatment restored the signaling pathway. Furthermore, CRS upregulated expression of proinflammatory cytokines in hippocampus, while p-CA reversed the CRS-induced effects. Our findings suggest that p-CA will offer therapeutic benefit to patients with stress-associated mental disorders.

The economics of aging with infectious and chronic diseases

We develop an economic model of aging in which the susceptibility and severity of infectious diseases depend on the accumulated health deficits (immunosenescence) and the life history of infections affects the accumulation of chronic health deficits (inflammaging). Individuals invest in their health to slow down health deficit accumulation and take measures to protect themselves from infectious diseases. We calibrate the model for an average American and explore how health expenditure, life expectancy, and the value of life depend on individual characteristics, medical technology, and the disease environment. We then use counterfactual computational experiments of the U.S. epidemiological transition 1860-2010 to show that the decline of infectious diseases caused a substantial decline of chronic diseases and contributed more to increasing life expectancy than advances in the treatment of chronic diseases.

Effect of Acute and Chronic Sleep Deficit on Working and Long-Term Memory in Rats

Effect of Acute and Chronic Sleep Deficit on Working and Long-Term Memory in Rats

Inhibiting CSF1R alleviates cerebrovascular white matter disease and cognitive impairment.

White matter abnormalities, related to poor cerebral perfusion, are a core feature of small vessel cerebrovascular disease, and critical determinants of vascular cognitive impairment and dementia. Despite this importance there is a lack of treatment options. Proliferation of microglia producing an expanded, reactive population and associated neuroinflammatory alterations have been implicated in the onset and progression of cerebrovascular white matter disease, in patients and in animal models, suggesting that targeting microglial proliferation may exert protection. Colony-stimulating factor-1 receptor (CSF1R) is a key regulator of microglial proliferation. We found that the expression of CSF1R/Csf1r and other markers indicative of increased microglial abundance are significantly elevated in damaged white matter in human cerebrovascular disease and in a clinically relevant mouse model of chronic cerebral hypoperfusion and vascular cognitive impairment. Using the mouse model, we investigated long-term pharmacological CSF1R inhibition, via GW2580, and demonstrated that the expansion of microglial numbers in chronic hypoperfused white matter is prevented. Transcriptomic analysis of hypoperfused white matter tissue showed enrichment of microglial and inflammatory gene sets, including phagocytic genes that were the predominant expression modules modified by CSF1R inhibition. Further, CSF1R inhibition attenuated hypoperfusion-induced white matter pathology and rescued spatial learning impairments and to a lesser extent cognitive flexibility. Overall, this work suggests that inhibition of CSF1R and microglial proliferation mediates protection against chronic cerebrovascular white matter pathology and cognitive deficits. Our study nominates CSF1R as a target for the treatment of vascular cognitive disorders with broader implications for treatment of other chronic white matter diseases.

Effect of Acute and Chronic Sleep Deficit on Working and Long-Term Memory in Rats

It is known that insufficient sleep or diurnal rhythm disturbances of sleep and wakefulness exert a detrimental effect on cognitive functions. It was thought for a long period that memory consolidation is the most vulnerable link, i.e., information transfer from short-term/working memory to long-term memory. However, there is a progressive number of studies indicating that the most negative consequences of sleep loss are observed in working memory. In our study, we undertook an effort to assess possible disturbances in working memory and long-term memory following sleep loss impact with different protocols in acute and chronic experiment in rats. Sleep in Wistar rats was deprived/restricted by swinging platform technique according to the following protocols: 1 – total sleep deprivation for 18 h; 2 – partial sleep restriction for 24 h (3 h of sleep deprivation alternated with 1 h of sleep opportunity – totally 18 h of sleep deprivation); 3 – chronic partial sleep restriction (conditions 2 for five consistent days). Total sleep deprivation in Y-maze test was shown to result in a significant decrease in spontaneous alternations of maze arms that indicates working memory impairment. This impact in Barnes test did not exert an effect on long-term memory – time spent for seeking a shelter did not change in this task. Acute and chronic sleep restriction induced no changes in working memory and long-term memory. The results obtained allow us to come to conclusion that working memory (in contrast to long-term memory) is a vulnerable component of cognitive function under total sleep deprivation conditions. This negative effect was abolished if periods of sleep deprivation alternated with short periods of sleep opportunities that indicate protective significance of short sleep periods for cognitive functions during sleep deficit. Hence, short-term sleep is helpful for cognitive health and protects working memory, whereas continuous long-term wakefulness impairs it.

In situ forming biomaterials as muscle void fillers for the provisional treatment of volumetric muscle loss injuries.

Volumetric muscle loss (VML) represents a devastating extremity injury which leads to chronic functional deficits and disability and is unrecoverable through normal healing pathways. When left untreated, the VML pathophysiology creates many challenges towards successful treatment, such as altered residual muscle architecture, excessive fibrosis, and contracture(s). As such, innovative approaches and technologies are needed to prevent or reverse these adverse sequelae. Development of a rationally designed biomaterial technology which is intended to be acutely placed within a VML defect - i.e., to serve as a muscle void filler (MVF) by maintaining the VML defect - could address this clinical unmet need by preventing these adverse sequelae as well as enabling multi-staged treatment approaches. To that end, three biomaterials were evaluated for their ability to serve as a provisional MVF treatment intended to stabilize a VML defect in a rat model for an extended period (28 days): polyvinyl alcohol (PVA), hyaluronic acid and polyethylene glycol combination (HA+PEG), and silicone, a clinically used soft tissue void filler. HA+PEG biomaterial showed signs of deformation, while both PVA and silicone did not. There were no differences between treatment groups for their effects on adjacent muscle fiber count and size distribution. Not surprisingly, silicone elicited robust fibrotic response resulting in a fibrotic barrier with a large infiltration of macrophages, a response not seen with either the PVA or HA+PEG. Taken together, PVA was found to be the best material to be used as a provisional MVF for maintaining VML defect volume while minimizing adverse effects on the surrounding muscle.

Anatomical Diversity of the Adult Corticospinal Tract Revealed by Single-Cell Transcriptional Profiling.

The corticospinal tract (CST) forms a central part of the voluntary motor apparatus in all mammals. Thus, injury, disease, and subsequent degeneration within this pathway result in chronic irreversible functional deficits. Current strategies to repair the damaged CST are suboptimal in part because of underexplored molecular heterogeneity within the adult tract. Here, we combine spinal retrograde CST tracing with single-cell RNA sequencing (scRNAseq) in adult male and female mice to index corticospinal neuron (CSN) subtypes that differentially innervate the forelimb and hindlimb. We exploit publicly available datasets to confer anatomic specialization among CSNs and show that CSNs segregate not only along the forelimb and hindlimb axis but also by supraspinal axon collateralization. These anatomically defined transcriptional data allow us to use machine learning tools to build classifiers that discriminate between CSNs and cortical layer 2/3 and nonspinally terminating layer 5 neurons in M1 and separately identify limb-specific CSNs. Using these tools, CSN subtypes can be differentially identified to study postnatal patterning of the CST in vivo, leveraged to screen for novel limb-specific axon growth survival and growth activators in vitro, and ultimately exploited to repair the damaged CST after injury and disease.SIGNIFICANCE STATEMENT Therapeutic interventions designed to repair the damaged CST after spinal cord injury have remained functionally suboptimal in part because of an incomplete understanding of the molecular heterogeneity among subclasses of CSNs. Here, we combine spinal retrograde labeling with scRNAseq and annotate a CSN index by the termination pattern of their primary axon in the cervical or lumbar spinal cord and supraspinal collateral terminal fields. Using machine learning we have confirmed the veracity of our CSN gene lists to train classifiers to identify CSNs among all classes of neurons in primary motor cortex to study the development, patterning, homeostasis, and response to injury and disease, and ultimately target streamlined repair strategies to this critical motor pathway.