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.

Mothers’challenges and experiences of children with cerebral palsy:a qualitative meta-synthesis

Objective:To examine what challenges and experiences a mother faces in caring for children with cerebral palsy(CP).As the main caregiver of children with CP,mothers are under multiple pressures.Even though mothers’challenges and experiences of children with CP will affect their quality of life and the rehabilitation of the children,little is known about their challenges and experiences during the whole care.Methods:A qualitative meta-synthesis was conducted to extract and analyze qualitative research from the PubMed,CINAHL,PsycINFO,Web of Science,Ovid and MEDLINE databases.Thirteen articles were selected and analyzed using thematic syntheses.Results:From 2522 screened abstracts,84 texts were reviewed,and 13 studies met the inclusion criteria.Mothers’challenges and experiences of children with CP include 4 themes,both positive and negative.Conclusions:The mothers of children with CP suffer from physical burden,as well as psychological pressure,in the care experience;social and healthcare support are their main challenges.Interventions to help them face the difficulties and adapt to the role of caregivers as soon as possible should target multiple aspects in order to maximize effectiveness,to promote the healthy growth of children with CP.

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.

Clinical Study on Improving Articulation Clarity in Spastic Cerebral Palsy with 120 Cases of Oral-Facial Acupressure Combined with Oral Placement Therapy

Objective:To observe the efficacy of oral-facial acupressure combined with oral placement therapy(OPT)in improving articulation clarity in 120 children with spastic cerebral palsy,and to explore effective therapeutic solutions for speech disorders associated with spastic cerebral palsy.Methods:A total of 120 children with spastic cerebral palsy and speech disorders,meeting the inclusion criteria,were randomly assigned into two groups:60 cases in the treatment group and 60 cases in the control group.The treatment group received orofacial acupressure combined with OPT,while the control group received only OPT.The Oral Motor Function Assessment Scale(OMFAS),developed by the China Rehabilitation Research Centre(CRRC),was used to evaluate the treatment outcomes before and after the intervention.Results:After the treatment,both the treatment and control groups showed improved mobility of the mandible,lips,and tongue.However,the treatment group exhibited significantly better improvement than the control group,with the difference between the two groups being statistically significant(P<0.05).Conclusion:Oral-facial acupressure combined with OPT can effectively improve articulation clarity in children with spastic cerebral palsy.This combined therapy is recommended for clinical promotion and application.

CLINICAL RESEARCH OF JIAJI(夹脊EX-B2) IN TREATMENT OF SPASTIC CEREBRAL PALSY WITH ACUPUNCTURE

Objective To observe the clinical therapeutic effects of Jiájǐ（夹脊EX-B2） on spastic cerebral palsy （SOP） with acupuncture.Methods 62 cases of SOP were randomized into two groups,named treat- ment group with acupuncture on Jiájǐ（夹脊EX-B2）,and control group with sham-acupuncture.The treatment was applied once a day,10 times made a course,totally 6 courses were required.Modified Ashworth scale and FIM grade were used to observe and assess the results of treatment.Results The total effective rate was 84.4 % in treatment group and was 63.3 % in control group,indicating significant difference （P〈0.01）. Conclusion Acupuncture on Jiájǐ（夹脊EX-B2） achieves good clinical therapeutic effects on SCP.

CURRENT SITUATION OF CHINESE REHABILITATION TREATMENT OF CEREBRAL PALSY

Analyze present situation of treatment of cerebral palsy at home and abroad, review in detail concrete methods and studies of mechanisms of acupuncture and moxibustion as main therapeutic way adopted at home, probe characteristics and models of Chinese rehabilitation treatment for cerebral palsy. Results indicate that acupuncture and moxibustion treatment of cerebral palsy has very great potential social and economic results. Therefore, it is appropriate to approach establishment of a comprehensive rehabilitation system of cerebral palsy with Chinese characteristics, and with acupuncture and moxibustion used as main way.

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.

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.

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.

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.

Ocular disorders in children with spastic subtype of cerebral palsy

AIM: To document common ocular abnormalities in children with spastic subtype of cerebral palsy (CP) and to find out whether any correlation exists between their occurance and etiologic factors.METHODS: Totally 194 patients with the diagnosis of spastic type CP were enrolled in this retrospective study. Detailed ophthalmic examinations were performed. Demographic data and neuroradiological findings were documented. Kruskal-Wallis, Mann Whitney U, Pearson Chi-square tests and Student’s t tests were used in the statistical analysis.RESULTS: The mean age was 64.7±44.2 months on the first ophthalmic examination. Prevalences of diplegia (47.4%) and tetraplegia (36.1%) were found to be higher than the frequency of hemiplegia (16.5% ) in our study population. Etiologic factor was asphyxia in 60.8% of the patients. Abnormal ocular findings were present in 78.9% of the patients. Statistically significant poor vision was detected in tetraplegia group among all the spastic ubtypes of CP (P =0.000). Anisometropia and significant refractive error were found in 14.4% and 70.1% of the patients, respectively. Thirty-six children (18.6% ) had nystagmus and 107 children (55.2% ) had strabismus. Lower gestational age and birth weight were statistically higher in patients with esotropia than exotropia (P=0.009 and P =0.024, respectively). Abnormal morphology of the optic disc was present in 152 eyes (39.2% ). Severe periventricular leukomalacia (PVL) was found in 48 patients and statistically significant poor vision was detected in the presence of PVL (P =0.000).CONCLUSION:Spastic diplegic or tetraplegic CP patients with positive neuroradiological symptoms, younger gestational age and lower birth weight ought to have detailed ophthalmic examinations as early as possible to provide best visual rehabilitation.·

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.

Gait analysis of children with spastic hemiplegic cerebral palsy

An experiment was carried out in the key laboratory for Technique Diagnosis and Function Assessment of Winter Sports of China to investigate the differences in gait characteristics between healthy children and children with spastic hemiplegic cerebral palsy. With permission of their parents, 200 healthy children aged 3 to 6 years in the kindergarten of Northeastern University were enrolled in this experiment. Twenty children aged 3 to 6 years with spastic hemiplegic cerebral palsy from Shengjing Hospital, China were also enrolled in this experiment. Standard data were collected by simultaneously recording gait information from two digital cameras. DVracker was used to analyze the standard data. The children with hemiplegic cerebra palsy had a longer gait cycle, slower walking speed, and longer support phase than did the healthy children. The support phase was longer than the swing phase in the children with hemiplegic cerebral palsy. There were significant differences in the angles of the hip, knee, and ankle joint between children with cerebral palsy and healthy children at the moment of touching the ground and buffering, and during pedal extension. Children with hemiplegic cerebral palsy had poor motor coordination during walking, which basically resulted in a short stride, high stride frequency to maintain speed, more obvious swing, and poor stability.

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.