Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

Multilevel analysis of the central-peripheral-target organ pathway:contributing to recovery after peripheral nerve injury

Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.

Role of copper in central nervous system physiology and pathology

Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous system.Central copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple sclerosis.This review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper availability.Overall,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.

Meningeal lymphatic vessel crosstalk with central nervous system immune cells in aging and neurodegenerative diseases

Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.

Microglia lactylation in relation to central nervous system diseases

The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

Heterogeneity of mature oligodendrocytes in the central nervous system

Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.

Human induced pluripotent stem cell-derived therapies for regeneration after central nervous system injury

In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained intriguing.Previous work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as neurons.While embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns remained.These barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem cells.The advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal subpopulations.The precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed differentiation.While the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma formation.Cells of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of success.Although the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor cells.Furthermore,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support integration.Lastly,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for immunosuppression.Translation to a clinical setting will involve careful consideration when assessing both physiologic and functional outcomes.This review will highlight both successes and challenges faced when using human induced pluripotent stem cell-derived cell transplantation therapies to promote endogenous regeneration.

High mobility group box 1 in the central nervous system:regeneration hidden beneath inflammation

High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.

Liposomes as versatile agents for the management of traumatic and nontraumatic central nervous system disorders:drug stability,targeting efficiency,and safety

Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic strategies.Liposomes are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and permeability.Therefore,they can potentially treat traumatic and nontraumatic central nervous system diseases.In this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics techniques.Afterwards,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain tumors.Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials.Additionally,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and safety.Therefore,we proposed development strategies related to liposomes to further promote their development in neurological disease research.

Prognostic factors for acute central retinal artery occlusion treated with hyperbaric oxygen:The Hong Kong study report number five

BACKGROUND Central retinal artery occlusion(CRAO)is a potentially blinding disease,and hyperbaric oxygen therapy(HBOT)is becoming increasingly popular with the support of scientific evidence.Despite the presence of various acute management measures,there is no clear evidence on the gold standard treatment for CRAO.AIM To identify factors and imaging parameters associated with good visual outcome,which guide ophthalmologists in the triage of CRAO patients for HBOT.METHODS Patients who suffered from CRAO and had a symptom onset≤6 h were recruited for a course of HBOT in a tertiary hospital after failing bedside treatment.Patient demographics,onset time,CRAO eye parameters,and past medical history were prospectively collected.Visual outcomes after HBOT were also analyzed.RESULTS A total of 26 patients were included;the female-to-male ratio was 1:1.6,and the mean age was 67.5 years±13.3 years(range 44–89 years).The mean duration of follow-up and mean visual acuity(VA)improvement were 10.0 mo±5.3 mo and 0.48 logarithm of minimal angle of resolution(logMAR)±0.57 logMAR(approx-imately 9 letters in ETDRS)(P=0.0001,Z=-3.67),respectively.The 1 mm zone of central macular thickness(CMT)on optical coherence tomography was not associated with VA changes(P=0.119);however,the 1-to-3 mm circular rim of CMT was fairly associated(P=0.02,Spearman's coefficient=0.45).Complete retinal perfusion time during fundus fluorescein angiography(FFA)was mode-rately associated(P=0.01,Spearman's coefficient=0.58)with visual outcome.

Genetically modified non-human primate models for research on neurodegenerative diseases

Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical settings.As the population ages,NDs are imposing a huge burden on public health systems and affected families.Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments.While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap.Old World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to humans.This is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience research.Recently,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms.This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.

Intranasal administration of stem cell-derived exosomes for central nervous system diseases

Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular communication.These nanosized vesicles transport internalized proteins,mRNA,miRNA,and other bioactive molecules.Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders.These exosomes exhibit multifaceted properties including antiapoptotic,anti-inflammatory,neurogenic,and vasculogenic effects.Furthermore,exosomes offer several advantages over stem cell therapy,such as high preservation capacity,low immunogenicity,the ability to traverse the blood-brain barrier,and the potential for drug encapsulation.Consequently,researchers have turned their attention to exosomes as a novel therapeutic avenue.Nonetheless,akin to the limitations of stem cell treatment,the limited accumulation of exosomes in the injured brain poses a challenge to their clinical application.To overcome this hurdle,intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous system.By exploiting the olfactory and trigeminal nerve axons,this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain barrier.Notably,exosomes,owing to their small size,can readily access the nerve pathways using this method.As a result,intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosomebased treatments.In this comprehensive review,we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system diseases.Furthermore,we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.

Petroleum geological characteristics and exploration targets of the oil-rich sags in the Central and West African Rift System

Based on seismic,drilling,and source rock analysis data,the petroleum geological characteristics and future exploration direction of the oil-rich sags in the Central and West African Rift System(CWARS)are discussed.The study shows that the Central African Rift System mainly develops high-quality lacustrine source rocks in the Lower Cretaceous,and the West African Rift System mainly develops high-quality terrigenous organic matter-rich marine source rocks in the Upper Cretaceous,and the two types of source rocks provide a material basis for the enrichment of oil and gas in the CWARS.Multiple sets of reservoir rocks including fractured basement and three sets of regional cap rocks in the Lower Cretaceous,the Upper Cretaceous,and the Paleogene are developed in the CWARS.Since the Late Mesozoic,due to the geodynamic factors including the dextral strike-slip movement of the Central African Shear Zone,the basins in different directions of the CWARS differ in terms of rifting stages,intervals of regional cap rocks,trap types and accumulation models.The NE-SW trending basins have mainly preserved one stage of rifting in the Early Cretaceous,with regional cap rocks developed in the Lower Cretaceous strata,forming traps of reverse anticlines,flower-shaped structures and basement buried hill,and two types of hydrocarbon accumulation models of"source and reservoir in the same formation,and accumulation inside source rocks"and"up-source and down-reservoir,and accumulation below source rocks".The NW–SE basins are characterized by multiple rifting stages superimposition,with the development of regional cap rocks in the Upper Cretaceous and Paleogene,forming traps of draping anticlines,faulted anticlines,antithetic fault blocks and the accumulation model of"down-source and up-reservoir,and accumulation above source rocks".The combination of reservoir and cap rocks inside source rocks of basins with multiple superimposed rifting stages,as well as the lithologic reservoirs and the shale oil inside source rocks of strong inversion basins are important fields for future exploration in basins of the CWARS.

Evidence of SARS-CoV-2 infection in pets,captive non-human primates and farm animals in Central Africa

It has been reported that the host of SARS-CoV-2 can be extremely wide due to the conservation of angiotensin converting enzyme 2 in mammals[1].Several studies have reported natural or experimental infection with SARS-CoV-2 in pets,farm and captive wild animals[2-4].However,to the best of our knowledge,there was no published study assessing virus circulation among domestic or captive animals in Central,West and East Africa.In this study,we assessed the presence and circulation of SARS-CoV-2 or other betacoronaviruses in pets,livestock and animals kept in captivity in conservation centers in Haut-Ogoouéprovince,southeastern Gabon.

Assessment of Wet Season Precipitation in the Central United States by the Regional Climate Simulation of the WRFG Member in NARCCAP and Its Relationship with Large-Scale Circulation Biases

Assessment of past-climate simulations of regional climate models(RCMs)is important for understanding the reliability of RCMs when used to project future regional climate.Here,we assess the performance and discuss possible causes of biases in a WRF-based RCM with a grid spacing of 50 km,named WRFG,from the North American Regional Climate Change Assessment Program(NARCCAP)in simulating wet season precipitation over the Central United States for a period when observational data are available.The RCM reproduces key features of the precipitation distribution characteristics during late spring to early summer,although it tends to underestimate the magnitude of precipitation.This dry bias is partially due to the model’s lack of skill in simulating nocturnal precipitation related to the lack of eastward propagating convective systems in the simulation.Inaccuracy in reproducing large-scale circulation and environmental conditions is another contributing factor.The too weak simulated pressure gradient between the Rocky Mountains and the Gulf of Mexico results in weaker southerly winds in between,leading to a reduction of warm moist air transport from the Gulf to the Central Great Plains.The simulated low-level horizontal convergence fields are less favorable for upward motion than in the NARR and hence,for the development of moist convection as well.Therefore,a careful examination of an RCM’s deficiencies and the identification of the source of errors are important when using the RCM to project precipitation changes in future climate scenarios.

Association between central serous chorioretinopathy and Helicobacter pylori infection: a systematic review and Meta-analysis

AIM:To investigate the association between central serous chorioretinopathy(CSC)and Helicobacter pylori(Hp)by summarizing all available evidence.METHODS:The Scopus,Embase,EBSCO,PubMed,Web of Science,and Cochrane Library databases for all relevant studies published from inception to October 2022 were searched,and manually searched for relevant reference lists as a supplement.Studies investigating the association between CSC and Hp infection were included.Finally,8 case-control studies were included in the Meta-analysis after study selection.RESULTS:The results showed no significant correlation between Hp infection and CSC[odds ratio(OR)1.89,95%confidential interval(CI)0.58–6.15,I2=96%,P=0.29].After subgroup analysis based on the degree of development of the study(developing/developed countries),it was found that the results of the two subgroups were the same as the whole,and no significant difference between the two subgroups existed.Meta-regression showed that the effect of sample size on heterogeneity among studies was more prominent(P<0.01,adjusted R^(2)=89.72%),which can explain 89.72%of the sources of heterogeneity.CONCLUSION:This Meta-analysis reveals no significant correlation between Hp infection and CSC,which still warrants further well-designed extensive sample studies to reach a more reliable conclusion and promote a better understanding of the treatment of CSC.

Crosstalk among mitophagy,pyroptosis,ferroptosis,and necroptosis in central nervous system injuries

Central nervous system injuries have a high rate of resulting in disability and mortality;however,at present,effective treatments are lacking.Programmed cell death,which is a genetically determined fo rm of active and ordered cell death with many types,has recently attra cted increasing attention due to its functions in determining the fate of cell survival.A growing number of studies have suggested that programmed cell death is involved in central nervous system injuries and plays an important role in the progression of brain damage.In this review,we provide an ove rview of the role of programmed cell death in central nervous system injuries,including the pathways involved in mitophagy,pyroptosis,ferroptosis,and necroptosis,and the underlying mechanisms by which mitophagy regulates pyroptosis,ferroptosis,and necro ptosis.We also discuss the new direction of therapeutic strategies to rgeting mitophagy for the treatment of central nervous system injuries,with the aim to determine the connection between programmed cell death and central nervous system injuries and to identify new therapies to modulate programmed cell death following central nervous system injury.In conclusion,based on these properties and effects,interventions targeting programmed cell death could be developed as potential therapeutic agents for central nervous system injury patients.

Oligodendrocytes in central nervous system diseases:the effect of cytokine regulation

Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines are involved in nearly every aspect of cellular functions such as migration, survival, proliferation, and differentiation. Oligodendrocytes are the myelin-forming cells in the central nervous system and play critical roles in the conduction of action potentials, supply of metabolic components for axons, and other functions. Emerging evidence suggests that both oligodendrocytes and oligodendrocyte precursor cells are vulnerable to cytokines released under pathological conditions. This review mainly summarizes the effects of cytokines on oligodendrocyte lineage cells in central nervous system diseases. A comprehensive understanding of the effects of cytokines on oligodendrocyte lineage cells contributes to our understanding of central nervous system diseases and offers insights into treatment strategies.

Labial inverse dilaceration of bilateral maxillary central incisors: A case report

BACKGROUND Dilaceration is a rare dental developmental anomaly characterized by an abrupt deviation along the longitudinal axis of the root in which an angulation forms between the root and the crown.Here,we report on dilacerated bilateral maxi-llary central incisors in mixed dentition.CASE SUMMARY A 10-year-old girl presented with a chief complaint of unerupted central incisors.An oral examination and radiography provided the basis for a diagnosis of dilaceration of the maxillary central incisors.After surgical exposure of the impacted teeth,a button with an attached chain was applied to the palatal surface of teeth 11 and 21.After 8 mo,a button was bonded to the labial surface of the crown to fix an elastic chain and move the teeth toward the maxillary arch.Finally,a fixed appliance was applied to tooth alignment to Class 1 malocclusion using a 0.019×0.025-inch nickel-titanium wire.After 3 years of follow-up,the clinical findings and radiographic assessment showed that the roots had developed with vital dental pulp and healthy periodontium,were acceptable aesthetically,and showed no resorption.CONCLUSION The rare occurrences of dilacerated bilateral maxillary central incisors can be successfully treated through surgical exposure and orthodontics.

Clinical Response to Treatment of Central Nervous System Tuberculosis in Non-Human Immunodeficiency Virus-Infected Adolescents and Adults

Introduction: More than half of patients with central nervous system tuberculosis (CNS TB) die or are left with severe neurological deficits despite receiving anti-TB treatment. Aims of the study: This study examined risk factors associated with poor response to initial treatment with four anti-TB drug regimens or three drug regimens with steroids as adjuvant therapy. Methods: This study analyzed medical records from two tertiary hospitals in Busan, Korea, between January 2009 and March 2012. The subjects were non-human immunodeficiency virus (HIV)-infected patients aged ≥16 years with clinical CNS TB. The subjects were divided into two groups according to response to treatment. Results: In totally, 52 patients with CNS TB were included. Of these, 14 (26%) and 38 (73%) showed poor and good responses, respectively. Of the patients with poor response, nine had stage III disease (64.3%) according to the British Medical Research Council (BMRC) staging system. A significantly higher proportion was seen in the good response group (p < 0.05). Patients with positive cerebrospinal fluid (CSF) acid-fast bacillus (AFB) culture, positive sputum AFB culture, positive CSF TB polymerase chain reaction (PCR) results, and brain tuberculoma had poorer responses (p < 0.05). Multivariate analysis to determine risk factors associated with poor response to anti-TB therapy revealed that a poor response was associated with stage III clinical signs upon diagnosis (odds ratio [OR] 32.122;95% confidence interval [CI] 2.221 - 464.605), positive sputum AFB culture (OR 13.624;95% CI 1.066 - 174.149), and tuberculoma on brain images (OR 45.714;95% CI 1.893 - 1104.018). Conclusions: The results demonstrate the importance of identifying the severity of CNS TB and promptly administering anti-TB drugs. It is necessary to perform drug susceptibility testing for anti-TB drugs. Further studies are needed to confirm the correlations between risk factors associated with poor response and anti-TB drug resistance and the other risk factors.