Genetic pathways in cerebral palsy:a review of the implications for precision diagnosis and understanding disease mechanisms

Ce rebral palsy is a diagnostic term utilized to describe a group of permanent disorders affecting movement and posture.Patients with cerebral palsy are often only capable of limited activity,resulting from non-progressive disturbances in the fetal or neonatal brain.These disturbances severely impact the child’s daily life and impose a substantial economic burden on the family.Although cerebral palsy encompasses various brain injuries leading to similar clinical outcomes,the unde rstanding of its etiological pathways remains incomplete owing to its complexity and heterogeneity.This review aims to summarize the current knowledge on the genetic factors influencing cerebral palsy development.It is now widely acknowledged that genetic mutations and alterations play a pivotal role in cerebral palsy development,which can be further influenced by environmental fa ctors.Des pite continuous research endeavors,the underlying fa ctors contributing to cerebral palsy remain are still elusive.However,significant progress has been made in genetic research that has markedly enhanced our comprehension of the genetic factors underlying cerebral palsy development.Moreove r,these genetic factors have been categorized based on the identified gene mutations in patients through clinical genotyping,including thrombosis,angiogenesis,mitochondrial and oxidative phosphorylation function,neuronal migration,and cellular autophagy.Furthermore,exploring targeted genotypes holds potential for precision treatment.In conclusion,advancements in genetic research have substantially improved our understanding of the genetic causes underlying cerebral palsy.These breakthroughs have the potential to pave the way for new treatments and therapies,consequently shaping the future of cerebral palsy research and its clinical management.The investigation of cerebral palsy genetics holds the potential to significantly advance treatments and management strategies.By elucidating the underlying cellular mechanisms,we can develop to rgeted interventions to optimize outcomes.A continued collaboration between researchers and clinicians is imperative to comprehensively unravel the intricate genetic etiology of cerebral palsy.

Allogeneic mesenchymal stem cells may be a viable treatment modality in cerebral palsy

BACKGROUND Cerebral palsy(CP)describes a group of disorders affecting movement,balance,and posture.Disturbances in motor functions constitute the main body of CP symptoms.These symptoms surface in early childhood and patients are affected for the rest of their lives.Currently,treatment involves various pharmacotherapies for different types of CP,including antiepileptics for epilepsy and Botox A for focal spasticity.However,none of these methods can provide full symptom relief.This has prompted researchers to look for new treatment modalities,one of which is mesenchymal stem cell therapy(MSCT).Despite being a promising tool and offering a wide array of possibilities,mesenchymal stem cells(MSCs)still need to be investigated for their efficacy and safety.AIM To analyze the efficacy and safety of MSCT in CP patients.METHODS Our sample consists of four CP patients who cannot stand or walk without external support.All of these cases received allogeneic MSCT six times as 1×106/kg intrathecally,intravenously,and intramuscularly using umbilical cord-derived MSCs(UC-MSC).We monitored and assessed the patients pre-and post-treatment using the Wee Functional Independence Measure(WeeFIM),Gross Motor Function Classification System(GMFCS),and Manual Ability Classification Scale(MACS)instruments.We utilized the Modified Ashworth Scale(MAS)to measure spasticity.RESULTS We found significant improvements in MAS scores after the intervention on both sides.Two months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046;four months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046;12 months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046.However,there was no significant difference in motor functions based on WeeFIM results(P>0.05).GMFCS and MACS scores differed significantly at 12 months after the intervention(P=0.046,P=0.046).Finally,there was no significant change in cognitive functions(P>0.05).CONCLUSION In light of our findings,we believe that UC-MSC therapy has a positive effect on spasticity,and it partially improves motor functions.

Effect of VOJTA Therapy on Gross Motor Function in Children with Cerebral Palsy

Objective: To investigate the effect of VOJTA therapy on gross motor function in children with cerebral palsy. Methods: The 86 children with cerebral palsy were all from the First People’s Hospital of Jingzhou City from January 2023-December 2023, and were divided into the control group and the study group with 43 cases according to the principle of voluntariness. Results: In terms of total effective rate of treatment, the gross motor function scale-88 (GMFM-88) was used to evaluate the effective rate before and after treatment, and the effective rate of the study group was higher than that of the control group, and the difference was statistically significant, and the scores of gross motor items of GMFM-88 were better than those of the control group after treatment, and the difference was statistically significant (P 0.05). Conclusion: The application of VOJTA therapy in the treatment of children with cerebral palsy can not only promote the rehabilitation of gross motor function, but also help to improve the treatment effect, and the earlier the treatment, the better.

An overview of acupuncture for the treatment of limb spasticity in cerebral palsy-A mini review

Cerebral palsy is a common chronic disabling disease in children with special needs,and rehabilitation for cerebral palsy is characterized by a long period,multiple methods and limited efficacy.Due to the limited motor function of cerebral palsy patients,the quality of life of patients is reduced,and their ability to participate in society is reduced,so the improvement of patients’motor function has become an important goal of cerebral palsy rehabilitation.The motor function of cerebral palsy has become an important goal of cerebral palsy rehabilitation.Limb spasticity is one of the main clinical signs of cerebral palsy patients,and the more severe the limb spasticity is,the greater the impact on the patient's motor function,so improving limb spasticity in patients with cerebral palsy is particularly important.Acupuncture,as a Chinese medicine treatment method,has been widely used in the clinical treatment of cerebral palsy in China,and has shown certain efficacy.To promote the clinical application of acupuncture technique in cerebral palsy limb spasticity,this paper analyses and summarizes the relevant literature on acupuncture treatment of cerebral palsy limb spasticity summarizes the current status of the clinical application of acupuncture in cerebral palsy limb spasticity,and provides clinical references for the reasonable application of acupuncture in cerebral palsy limb spasticity.

Effects of video game-based therapy in an adolescent with cerebral palsy: A case report

BACKGROUND Herein,we report the case of a 13-year-old boy with spastic quadriplegia cerebral palsy(CP)at Gross Motor Function Classification System(GMFCS)level II,en-gaging in a 6-wk video game-based therapy(VBT)program.This study aimed to offer essential insights regarding VBT’s impact on enhancing the physical function and improving the quality of life(QoL)of adolescents diagnosed with CP.This report provides a distinctive viewpoint that can inform and direct future clinical practices and research endeavors.CASE SUMMARY The boy presented with moderate mobility,balance,and overall well-being.He faced challenges with diminished lower limb strength,which affected his daily living and physical fitness capabilities.Our participant was diagnosed with spas-tic quadriplegic CP at GMFCS level II.He participated in a 6-wk program of VBT using a play station.This innovative approach incorporates warm-up exercises,interactive activities,and cool-down routines,targeting various movements,in-cluding single-leg stance,weight shifting,kicking,jumping,marching,and squatting.After VBT,the strength of the left hip extensor significantly increased from 199.3 N to 541.3 N.Distance covered as part of a 6-min walk test increased by 82 m.His Paediatric QoL Inventory score increased dramatically by 25.9%.CONCLUSION VBT is an innovative,individualized therapy that enhances physical function and QoL in CP,emphasizing its role in ambulatory patients.

Precise Rehabilitation Strategies for Functional Impairment in Children with Cerebral Palsy

This paper explores the effect of precise rehabilitation strategies under the international classification of functioning,disability and health for children and youth(ICF-CY)on the motor function of children with cerebral palsy.Under the framework of ICF-CY,the observation team is designed and evaluated from physical functions,activities and participation,environmental factors,and devel-ops individualized rehabilitation strategies that are tailored to individual character-istics.The control group was assessed by traditional methods and treatment plans and measures were formulated and guided.The course of treatment was 12 months.The scores of GMFM-88,Peabody Motor Development Scale-2con-cluding fine motor quotient(PDMS-FM),WeeFIM and the ability of daily living(ADL)scale(Barthel index,BI)score were compared before and after treatment.The research shows that precise rehabilitation strategy mode for children with cer-ebral palsy under the ICF-CY framework can effectively improve the motor func-tion and the ability of daily living(ADL)in children with cerebral palsy.Rehabilitation evaluation and treatment mode of children with cerebral palsy under ICF-CY framework can effectively improve the gross motor function of children with cerebral palsy.Individualized evaluation and analysis and guidance of comprehensive rehabilitation treatment have certain advantages.The overall treatment effect is better than that of traditional rehabilitation evaluation.

Systematic evaluation of the efficacy and safety of botulinum toxin type A in the treatment of spastic cerebral palsy

Background:Botulinum toxin type A(BTX-A)is a neuromuscular blocking agent.BTX-A inhibits acetylcholine release,causes neuromuscular transmission impairment,and decreases muscle spasms.Objective:To explore the efficacy and safety of BTX-A injection in the treatment of spastic cerebral palsy through systematic evaluation and to provide a reference for the clinical use of BTX-A.Methods:We used“Cerebral palsy”and“BTX-A”as the subject terms and used a combination of subject terms and free words for the search.We searched 7 databases,including CNKI,Wanfang,VIP,Sinomed,PubMed,Embase,and Web of science.Based on the inclusion and exclusion criteria,we screened the articles by reading their titles,abstracts,and full texts and finally included relevant literature for systematic evaluation.Result:A total of 93 papers were systematically evaluated,revealing that BTX-A injection treatment can effectively reduce muscle tone,increase joint mobility,improve gait and motor posture,and enhance gross motor movements in patients with spastic cerebral palsy.The benefits of BTX-A treatment can be sustained for 3–6 months,with motor ability improvement lasting up to 1 year.Combining BTX-A treatment with rehabilitation or external fixation therapy can enhance its efficacy.However,the effectiveness of BTX-A treatment is influenced by several factors,such as the dosage,number of injections,and patient age.Adverse reactions to BTX-A treatment are typically mild and can be relieved within 1–2 weeks.Conclusion:BTX-A injection is relatively safe but reversible.

Effect of Lumbar Spinal Point Injection on Sitting Function in Children with Cerebral Palsy

Objective: To observe the effect of lumbar spinal point injection on sitting function in children with cerebral palsy. Method: Sixty-two children with post-confirmed cerebral palsy were randomly divided into control group and treatment group, 31 each. The control group was given conventional rehabilitation treatment, and the treatment group was given lumbar chiropspinal acupoint injection on the basis of the treatment method of the control group. After 3 consecutive courses of treatment, the sitting score of the two groups before and after treatment (GMFM88) was used to evaluate the sitting score before and after treatment. Outcome: Before treatment, the two groups were evaluated and the differences were not statistically significant (p > 0.05), which was comparable. The two groups (GMFM88) after treatment had significantly increased the differential values, and the difference was statistically significant compared with the same group before treatment (p Conclusion: Conventional rehabilitation combined with lumbar spinal point injection can effectively improve the sitting motor function of children with cerebral palsy.

Research progress regarding the nutritional status and assessment methods of cerebral palsy patients

Cerebral palsy is a group of clinical disorders characterized by persistent central motor deficits and postural abnormalities due to non-progressive damage to the fetal or infant brain.Malnutrition is one of the most common clinical comorbidities in children with cerebral palsy and is the result of a combination of internal factors,such as the child’s structural and functional abnormalities,and external factors,such as the child’s feeding habits and family/social factors.The nutritional status of children with cerebral palsy is closely related to their development,quality of life,social participation,and life expectancy;thus,an objective and accurate understanding of the nutritional status of these children through rehabilitation assessment is essential for their growth and development.The current nutritional assessments include routine measurements of human nutritional parameters,scale-based assessments,and instrumental assessments.It is important to detect malnutrition in children with cerebral palsy at an early stage,reduce the prevalence of malnutrition,and improve the quality of survival.Therefore,this review aimed to analyze and summarize the nutritional status and assessment methods of children with cerebral palsy,to assess the nutritional status of children with cerebral palsy from multiple perspectives,indicators and directions,and to provide reference for the early detection of co-morbid malnutrition in children with cerebral palsy.

A Randomised Controlled Study to Investigate Effects of Bobath Based Trunk Control Training on Motor Function of Children with Spastic Bilateral Cerebral Palsy

Purpose: The aim of this study was to investigate the effects of trunk control on motor function, which plays an important role in the daily activities of children with Cerebral Palsy (CP) and is often observed as a deficiency in children with CP. Material and Methods: Forty children with spastic bilateral CP, ages between 3 to 10 years and with Gross Motor Function Classification System (GMFCS) level I, II, and III were included in this study. Children were divided into two groups using randomization and in training group;Bobath Therapy for trunk control in addition to classical physiotherapy programs was performed for 45 minutes, for two days a week, for 6 weeks. In control group, existing physiotherapy program, 45 minutes for two days a week, continued. Any addition was not made into the existing program of the control group. Modified Ashworth Scale (MAS), Pediatric Berg Balance Scale (PBBS), Trunk Control Measurement Scale (TCMS), 1 Minute Walking Test (1MWT), Timed Up and Go Test (TUG) were applied to both groups before and after 6 weeks. Moreover, trunk muscle strength of children was evaluated. Results: After therapy, differences were found in results of MAS and PBBS, and trunk extensor strength between the training group and the control group in favor of the training group (p Conclusion: This study shows that adding exercises which aim trunk to conventional physiotherapy and exercise programs of children with CP, affects motor function positively.

Research progress of Chinese and Western medicine on spastic cerebral palsy in children in recent ten years

In recent ten years,with more and more children with spastic cerebral palsy appearing around us,relevant clinical research has also become a research hotspot.However,at present,there is no radical plan for the treatment of children with spastic cerebral palsy in the world.This study summarizes the latest progress of traditional Chinese and Western medicine in the treatment of children with spastic cerebral palsy in recent years,hoping that the whole work can serve as a clinical and theoretical basis and provide certain reference significance.

Acupuncture for cerebral palsy: a meta-analysis of randomized controlled trials

OBJECTIVE： To evaluate the efficacy and safety of acupuncture therapy for children with cerebral palsy. DATA SOURCES： We conducted electronic searches of PUBMED（1950/2017）, EMBASE（1974/2017）, Science Direct（1986/2017）, Academic Source Premier（1887/2017）, the Cochrane Library（Issue 4, April 2017）, Science Citation Index Expanded（1900/2017）, China National Knowledge Infrastructure（1915/2017）, China Biological Medicine（1990/2017-04）, Wan Fang（1980/2017）, VIP（1989/2017）, and Chinese Science Citation Database（1989/2017）. DATA SELECTION： We included randomized controlled trials that aimed to compare the effect of acupuncture plus rehabilitation training versus rehabilitation training alone. Data about functional motor abilities, daily activity/social participation, effective rate, intellectual development, and adverse effects were included. We used Revman 5.2 software for statistical analysis. OUTCOME MEASURES： The primary outcomes included functional motor abilities, daily activity, and effective rate. The secondary outcomes included intellectual development and adverse effects.RESULTS： Twenty-one studies with a total of 1718 participants met the inclusion criteria. The effect size of gross motor function（SMD = 0.64, 95% CI： 0.52 to 0.76, P 〈 0.00001; I^2 = 0%, P = 0.69; in 13 studies with 1144 patients） and the total effective rate（RR = 1.28, 95% CI： 1.20 to 1.37, P 〈 0.00001; I^2 = 18%, P = 0.27; in 12 studies with 1106 patients） suggested that acupuncture plus rehabilitation produced a significant improvement in gross motor function and a high total effective rate. The pooled fine motor function（SMD = 3.48, 95% CI： 2.62 to 4.34, P 〈 0.00001; I^2 = 64%, P = 0.10; in 2 studies with 193 patients）, modified Ashworth scale scores（SMD = –0.31, 95% CI： –0.52 to –0.11, P = 0.003; I^2 = 74%, P = 0.004; in 5 studies with 363 patients） and activities of daily living（SMD = 1.45, 95% CI： 1.20 to 1.71, P 〈 0.00001; I^2 = 78%, P = 0.004; in 4 studies with 313 patients） also indicated improvements in children with cerebral palsy. Publication bias was not observed. Only mild adverse events related to acupuncture were reported. CONCLUSION： Acupuncture plus rehabilitation training improved gross motor function, reduced muscle spasms, and enhanced daily life activities in children with cerebral palsy. However, this conclusion should be interpreted with caution due to the small number of randomized controlled trials available and the small sample sizes. More high-quality and large-scale studies are needed.

Motor function outcomes of pediatric patients with hemiplegic cerebral palsy after rehabilitation treatment:a diffusion tensor imaging study

Previous diffusion tensor imaging （DTI） studies regarding pediatric patients with motor dys-function have conifrmed the correlation between DTI parameters of the injured corticospinal tract and the severity of motor dysfunction. There is also evidence that DTI parameters can help predict the prognosis of motor function of patients with cerebral palsy. But few studies are re-ported on the DTI parameters that can relfect the motor function outcomes of pediatric patients with hemiplegic cerebral palsy after rehabilitation treatment. In the present study, 36 pediatric patients with hemiplegic cerebral palsy were included. Before and after rehabilitation treatment, DTI was used to measure the ifber number （FN）, fractional anisotropy （FA） and apparent dif-fusion coefifcient （ADC） of bilateral corticospinal tracts. Functional Level of Hemiplegia scale （FxL） was used to assess the therapeutic effect of rehabilitative therapy on clinical hemiplegia. Correlation analysis was performed to assess the statistical interrelationship between the change amount of DTI parameters and FxL. DTI ifndings obtained at the initial and follow-up evalua-tions demonstrated that more affected corticospinal tract yielded signiifcantly decreased FN and FA values and signiifcantly increased ADC value compared to the less affected corticospinal tract. Correlation analysis results showed that the change amount of FxL was positively correlated to FN and FA values, and the correlation to FN was stronger than the correlation to FA. The results suggest that FN and FA values can be used to evaluate the motor function outcomes of pediatric patients with hemiplegic cerebral palsy after rehabilitation treatment and FN is of more signiif-cance for evaluation.

Differences in standing balance between patients with diplegic and hemiplegic cerebral palsy

Maintaining standing postural balance is important for walking and handling abilities in patients with cerebral palsy. This study included 23 patients with cerebral palsy （seven with spastic diplegia and 16 with spastic hemiplegia）, aged from 7 to 16 years of age. Standing posture balance measurements were performed using an AMTI model OR6-7 force platform with the eyes open and closed. Patients with diplegic cerebral palsy exhibited greater center of pressure displacement areas with the eyes open and greater center of pressure sway in the medial-lateral direction with the eyes open and closed compared with hemiplegic patients, Thus, diplegic patients exhibited weaker postural balance control ability and less standing stability compared with hemiplegic cerebral palsy patients.

Establishing a rat model of spastic cerebral palsy by targeted ethanol injection

Spastic cerebral palsy is generally considered to result from cerebral cortical or pyramidal tract damage. Here, we precisely targeted the left pyramidal tract of 2-month-old Sprague-Dawley rats placed on a stereotaxic instrument under intraperitoneal anesthesia. Based on the rat brain stereotaxic map, a 1-mm hole was made 10 mm posterior to bregma and 0.8 mm left of sagittal suture. A microsyringe was inserted perpendicularly to the surface of the brain to a depth of 9.7 mm, and 15 wL of ethanol was slowly injected to establish a rat model of spastic cerebral palsy. After modeling, the rats appeared to have necrotic voids in the pyramidal tract and exhibited typical signs and symptoms of flexion spasms that lasted for a long period of time. These findings indicate that this is an effective and easy method of establishing a rat model of spastic cerebral palsy with good reproducibility. Ethanol as a chemical ablation agent specifically and thoroughly damages the py- ramidal tract, and therefore, the animals display flexion spasms, which are a typical symptom of the disease.

Progress in clinical trials of stem cell therapy for cerebral palsy

Cerebral palsy is the most common disease in children associated with lifelong disability in many countries.Clinical research has demonstrated that traditional physiotherapy and rehabilitation therapies cannot alone cure cerebral palsy.Stem cell transplantation is an emerging therapy that has been applied in clinical trials for a variety of neurological diseases because of the regenerative and unlimited proliferative capacity of stem cells.In this review, we summarize the design schemes and results of these clinical trials.Our findings reveal great differences in population characteristics, stem cell types and doses, administration methods, and evaluation methods among the included clinical trials.Furthermore, we also assess the safety and efficacy of these clinical trials.We anticipate that our findings will advance the rational development of clinical trials of stem cell therapy for cerebral palsy and contribute to the clinical application of stem cells.

Therapeutic effects on spastic cerebral palsy in children Acupuncture and massage at the Shu and He acupoints versus routine acupoints

BACKGROUND： Based on clinical findings and syndromes, it has been previously shown that therapeutic methods for cerebral palsy can be greatly improved by selecting fewer, but more accurate acupoints. Therefore, greater therapeutic efficacy for cerebral palsy could be obtained by selecting the five Shu acupoints, which are located at the qi-intersecting point of the twelve meridians below the elbow and knee. OBJECTIVE： To treat children with spastic cerebral palsy using acupuncture and massage at the Shu and He points through a combination of rehabilitative training, and to compare the effects with routine acupuncture and massage. DESIGN： A randomized controlled clinical trial. SETTING： Rehabilitation Center for Cerebral Palsy, Department of Pediatrics, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine. PARTICIPANTS： Sixty children with spastic cerebral palsy were selected from the Rehabilitation Center for Cerebral Palsy, Department of Pediatrics, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from May 2003 to February 2006. There were 38 boys and 22 girls, aged 10 months to 4 years old, muscle strength ranging from grade I to grade IV. The children were randomly divided into a treatment group （n =30） and a control group （n =30）. Informed consent for the therapeutic program was obtained from the relatives of all enrolled children. The study was approved by the Hospital＇s Ethical Committee. METHODS： All children were given exercise and occupational therapy based on standard treatments. （1） In the control group, the children were additionally treated with routine acupuncture and massage during the one-month basic rehabilitative training. The acupuncture needles were manipulated alternately at the acupoints of Jianyu, Shousanli, Binao, Hegu, Huantiao, Xuanzhong, and Biguan. They were treated once per day, 6 days a week, followed by one day of rest. The children＇s limbs were first massaged by pressing, stretching, rolling, and kneading. Then, the same acupuncture points were pressed with the thumb for 30 minutes each time, once a day, 6 days a week, followed by one day of rest. The treatment continued for 1 month. （2） In the treatment group, the children were administered acupuncture and massage at the Shu and He points during the one-month basic rehabilitative treatment. For acupuncture of the upper limbs, the following acupoints were used： Sanjian and Quchi of the Large Intestine Meridian of Hand-Yangming, and Houxi and Xiaohai of the Small Intestine Meridian of Hand-Taiyang. The acupoints were acupunctured alternately every other day. For acupuncture of the lower limbs, the following acupoints were used; Zulinqi and Yanglingquan of the Gall bladder Meridian of Foot-Shaoyang, Taibai and Yinlingquan of the Spleen Meridian of Foot-Taiyang, or Xiangu and Zusanli of the Stomach Meridian of Foot-Yangming. The acupoints were acupunctured alternately every other day. Three needles were for the medial malleolus and three needles for the lateral malleolus. They were treated once a day, 6 days a week, followed by one day of rest. The children＇s limbs were first massaged by means of pressing, stretching, rolling, and kneading. The same acupuncture points were then pressed with the thumb for 0.5-1 minute at each point, 30 minutes each time, once a day, 6 days a week, followed by one day of rest. MAIN OUTCOME MEASURES： Therapeutic efficacy was evaluated using gross motor function measurements, as well as activity of daily living scale before and after treatment. RESULTS： All 60 enrolled children with spastic cerebral palsy were included in the final analysis of results. （1） Comparison of gross motor function scores： The gross motor function score after treatment was significantly higher in both the treatment group and control group than before treatment （t = -3.86 and -8.882, respectively, P 〈 0.05）. The scores in the treatment group were significantly higher than the control group scores （t = -7.166, P 〈 0.01）. （2） Changes in activity of daily living scores： The scores for activity of daily living in the treatment group was significantly higher after treatment than before treatment （t = -3.933, P 〈 0.01）, and was also significantly higher than the control group （t = -0.671, P 〈 0.05）. CONCLUSION： Acupuncture and massage at the Shu and He acupoints can significantly ameliorate motor function deficits and movement disabilities in children with spastic cerebral palsy. The therapeutic efficacy at these acupoints is better than routine acupuncture and massage.

An animal model of cerebral palsy induced by prenatal exposure to lipopolysaccharide and hypoxia

BACKGROUND： Neonatal cerebral palsy is mainly caused by prenatal factors. At present, an animal model of prenatal infection and early postnatal hypoxia does not exist. OBJECTIVE： To observe morphology and motor performance following prenatal infection and hypoxic insult-induced brain damage of neonatal rats to verify the feasibility to establish a model of cerebral palsy. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratories of Xinjiang Center for Disease Control and Prevention from September 2007 to June 2008. MATERIALS： The hypoxic incubator was purchased from Shanghai Pediatric Medical Institute, China. Lipopolysaccharide （LPS, Escherichia coil, 055： B5） was purchased from Sigma-Aldrich （St. Louis, MO, USA）. METHODS： A total of 27 Wistar rats, aged 7 days, were randomly assigned to sham-surgery group （n = 15） with no carotid artery incision or hypoxia treatment, hypoxia/ischemia （H/I） group （n = 12） undergoing ligature of the right common carotid artery followed by exposure to hypoxia at postnatal day 7 （P7）, and LPS/H group （n = 19）, in which pregnant rats were exposed in utero to LPS followed by prenatal hypoxia at embryonic day 16. MAIN OUTCOME MEASURES： Behavior, compound muscle action potential, and pathological changes were observed in 28-day-old rats. RESULTS： The footprint repeat space showed that left limb footprint repeatability in the H/I and LPS/H groups was lower than in the sham-surgery group （P 〈 0.05）. The space between the footprints was larger and unstable. Hind limb quadricep compound muscle action potential in the H/I and LPS/H groups showed lower wave amplitude compared with the sham-surgery group （P〈 0.05） Hematoxylin and eosin staining showed irregular cells around the ventricle, as well as periventricular leukomalacia. CONCLUSION： An animal model of cerebral palsy was established, which simulated the human condition most likely associated with occurrence of this disease. This model could be used for experimental studies related to cerebral palsy.

Response of the sensorimotor cortex of cerebral palsy rats receiving transplantation of vascular endothelial growth factor 165-transfected neural stem cells

Neural stem cells are characterized by the ability to differentiate and stably express exogenous ge- nes. Vascular endothelial growth factor plays a role in protecting local blood vessels and neurons of newborn rats with hypoxic-ischemic encephalopathy. Transplantation of vascular endothelial growth factor-transfected neural stem cells may be neuroprotective in rats with cerebral palsy. In this study, 7-day-old Sprague-Dawley rats were divided into five groups： （1） sham operation （control）, （2） cerebral palsy model alone or with （3） phosphate-buffered saline, （4） vascular en- dothelial growth factor 165 ＋ neural stem cells, or （5） neural stem cells alone. The cerebral palsy model was established by ligating the left common carotid artery followed by exposure to hypox- ia. Phosphate-buffered saline, vascular endothelial growth factor ＋ neural stem cells, and neural stem cells alone were administered into the sensorimotor cortex using the stereotaxic instrument and microsyringe. After transplantation, the radial-arm water maze test and holding test were performed. Immunohistochemistry for vascular endothelial growth factor and histology using hematoxylin-eosin were performed on cerebral cortex. Results revealed that the number of vas- cular endothelial growth factor-positive cells in cerebral palsy rats transplanted with vascular endothelial growth factor-transfected neural stem cells was increased, the time for finding water and the finding repetitions were reduced, the holding time was prolonged, and the degree of cell degeneration or necrosis was reduced. These findings indicate that the transplantation of vascu- lar endothelial growth factor-transfected neural stem cells alleviates brain damage and cognitive deficits, and is neuroprotective in neonatal rats with hypoxia ischemic-mediated cerebral palsy.

Mononuclear cells from the cord blood and granulocytecolony stimulating factor-mobilized peripheral blood:is there a potential for treatment of cerebral palsy?

To investigate a possible therapeutic mechanism of cell therapy in the field of cerebral palsy using granulocyte-colony stimulating factor（G-CSF）-mobilized peripheral blood mononuclear cells（m PBMCs）,we compared the expression of inflammatory cytokines and neurotrophic factors in PBMCs and m PBMCs from children with cerebral palsy to those from healthy adult donors and to cord blood mononuclear cells donated from healthy newborns.No significant differences in expression of neurotrophic factors were found between PBMCs and m PBMCs.However,in cerebral palsy children,the expression of interleukin-6 was significantly increased in m PBMCs as compared to PBMCs,and the expression of interleukin-3 was significantly decreased in m PBMCs as compared to PBMCs.In healthy adults,the expression levels of both interleukin-1βand interleukin-6 were significantly increased in m PBMCs as compared to PBMCs.The expression of brain-derived neurotrophic factors in m PBMC from cerebral palsy children was significantly higher than that in the cord blood or m PBMCs from healthy adults.The expression of G-CSF in m PBMCs from cerebral palsy children was comparable to that in the cord blood but significantly higher than that in m PBMCs from healthy adults.Lower expression of pro-inflammatory cytokines（interleukin-1β,interleukin-3,and-6）and higher expression of anti-inflammatory cytokines（interleukin-8 and interleukin-9）were observed from the cord blood and m PBMCs from cerebral palsy children rather than from healthy adults.These findings indicate that m PBMCs from cerebral palsy and cord blood mononuclear cells from healthy newborns have the potential to become seed cells for treatment of cerebral palsy.