Successful Outcome of Patellectomy Plus Chemotherapy for Primary Bone Lymphoma of the Patella: A Case Report and Literature Review.

Primary bone lymphoma (PBL) is a rare but distinct clinicopathological disease, usually occurring in the pelvis, spine, and ribs. To date, only a few cases have been reported as beginning in the patella. Due to the lack of clinical evidence, the optimal treatment strategy has not been established. Here, we report a case that presented unexplained right knee pain. The case was diagnosed with the non-germinal center, diffuse large B cell lymphoma in the patella by imaging examinations and bone biopsy. Then, the patient received a patellectomy and eight cycles of R-CHOP chemotherapy. After treatment, the patient achieved a favorable prognosis and satisfactory functional recovery.

Mechanism and prognostic indicators for explosion-related eye trauma: eye injury vitrectomy study.

PURPOSE: To explore the clinical features, surgical interventions and prognosis of injured eyes following explosion and to develop the risk factors for poor prognosis. METHODS: A nested case-control study. To the date of 31 December 2018, 99 explosion-related eye globes were selected from the Eye Injury Vitrectomy Study database, which is a multicenter prospective cohort study and began in 1990s. All cases selected underwent vitreoretinal surgery or enucleation and were followed up for at least 6 months. Clinically meaningful preoperative variables and outcomes were used to develop logistic regression models. RESULTS: The unfavourable outcomes were defined as silicone oil-filled eyes, phthisis bulbi, enucleation and anatomically restored eyes whose final BCVA is worse than initial vision after 6 months of follow-up. The proportion of unfavourable outcomes was 92.0%, 60.9% and 66.7% in large festive fireworks, detonator and beer bottle groups respective. The anatomic and visual outcome of injured eyes with combined injury of blast wave and projectile were worse than that of ruptured eyes (Fisher's exact = 0.041). The extrusion of iris/lens (OR = 3.20, p = 0.015), PVR-C (OR = 6.08, p = 0.036) and choroid damage (OR = 5.84, p = 0.025) is independent risk factors of unfavourable prognosis for explosion-related eye trauma. CONCLUSION: The extrusion of iris/lens, PVR-C and choroid damage is the independent risk factors for unfavourable outcomes in explosion-related eye trauma. There is a unique injury mechanism in explosion-related eye trauma. SUMMARY STATEMENT: Through the nested case-control study, the extrusion of iris/lens, PVR-C, and choroid damage are the independent risk factors for unfavorable outcomes in explosion-related eye trauma. The mechanism of open globe mixture and close globe mixture in explosion-related eye trauma need more cases and participating units to explore together in the future.

Prognostic factors and long-term outcomes of eye-globe perforation: Eye injury vitrectomy study.

PURPOSE: To delineate anatomic and visual outcomes of injured eye globes with perforating, and to develop the prognostic indicators for perforating eyes. METHODS: The case series study, from a multicenter prospective cohort database. To the date of December 31st, 2018, of 63 perforating globes were selected. All cases underwent vitreoretinal surgeries or enucleations, and were followed up for at least 6 months. Demographic characteristics, basic examination for traumatized eyes, and intraocular tissue damages were recorded by surgery-in-chief. At the follow-up visit, best corrected VA, intraocular pressure, the intraocular tamponade material, retinal anatomic outcome of eye-globes, and phthisis or enucleation were evaluated. RESULTS: Fifty injured eyes (79%) were caused by sharp objects and 13 eyes (21%) were injured by a missiles. Twenty-two injured eyes can be anatomically restored with final vision of more than 4/200 through vitreoretinal surgery. The PVR-C (OR = 5.67, P = 0.01), area of retinectomy more than 2 times of optic disk (OR = 5.16, P = 0.04), and macular damage (OR = 6.38, P = 0.01) were correlated with unfavorable outcomes. CONCLUSION: The injured eyes with perforation can be saved through vitreoretinal surgery, the PVR-C, retinectomy more than 2 times of optic disk, and macular damage were independent risk factors for poor long-term prognosis.

Traumatic choroidal injuries - classification, incidence, diagnosis and prognosis twenty-year results of Eye Injury Vitrectomy Study.

PURPOSE: To characterize the classification, incidence, diagnosis and prognosis of traumatic choroidal injuries. METHODS: Subjects were selected from the database of the Eye Injury Vitrectomy Study (EIVS) and were examined for occurrences of different categories of choroidal injuries. Standard photographs were collected. Anatomical and visual outcomes were assessed in patients with greater than 1 year of follow-up. Eyes that had no light perception (NLP) and/or phthisis bulbi were defined as having had unfavourable outcomes. The percentage of eyes with an unfavourable outcome was analysed for different types of choroidal injuries. RESULTS: Nine categories of choroidal injuries with distinctive features were identified in the EIVS database. The incidence and the percentage of eyes with an unfavourable outcome in each injury category were as follows: suprachoroidal effusion, 21.2% (7.2%); suprachoroidal haemorrhage, 12.8% (11.2%); massive suprachoroidal haemorrhage, 4.0% (64.9%); choroidal avulsion, 4.2% (92.2%); traumatic chorioretinal rupture, 1.8% (13.3%); choroidal rupture, 4.8% (6.8%); choroidal loss, 1.6% (79.3%); choroidal hole, 1.1% (5.3%); and choroidal damage at the wound site, 39.2% (17.7%). CONCLUSIONS: Ocular trauma can cause a variety of choroidal injuries that have distinctive features, some of which are associated with a high frequency of unfavourable prognoses.

Evaluation of Lateral-Flow Assay for Rapid Detection of Influenza Virus.

BACKGROUND: Influenza virus mainly causes acute respiratory infections in humans. However, the diagnosis of influenza is not accurate based on clinical evidence, as the symptoms of flu are similar to other respiratory virus. The lateral-flow assay is a rapid method to detect influenza virus. But the effectiveness of the technique in detecting flu viruses is unclear. Hence, a meta-analysis would be performed to evaluate the accuracy of LFA in detecting influenza virus. METHODS: Relevant literature was searched out in PubMed, Embase, Web of Science, and Cochrane Library databases with the keywords "lateral flow assay" and "flu virus". By Meta-DiSc software, pooled sensitivity, pooled specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), summary receiver operating characteristic curve (SROC), and area under the curve (AUC) can be calculated. RESULTS: This meta-analysis contains 13 studies and 24 data. The pooled sensitivity and specificity of the influenza virus detected by LFA were 0.84 (95% CI: 0.82-0.86) and 0.97 (95% CI: 0.97-0.98), respectively. The pooled values of PLR, NLR, DOR, and SROC were 32.68 (17.16-62.24), 0.17 (0.13-0.24), 334.07 (144.27-773.53), and 0.9877. No publication bias was found. CONCLUSIONS: LFA exhibited high sensitivity and specificity in diagnosing influenza virus. It is a valuable alternative method which can diagnose influenza virus quickly. However, more evidence is required to confirm whether LFA is comparable to traditional methods for detecting the virus.

GPR17 plays a role in ischemia-induced endogenous repair of immature neonatal cerebral White matter.

Whether GPR17 has the same distribution and repair mechanism in immature white matter with periventricular leukomalacia (PVL) as in the adult brain remains to be determined. This study tried to explore the expression phase and site of GPR17, and to investigate the effect of silencing GPR17 on endogenous repair mechanism of immature white matter with PVL. Ischemic PVL in vivo results showed that GPR17 gene and protein expression increased more in the PVL than in the sham group at 12 h-24 h and 72h to 7 days after PVL. NG2+/GPR17+progenitor cells at 48 h-96 h and O4+/GPR17+precursor cells at 72h to 7d were also significantly increased in the PVL compared to the sham groups. Results in vitro showed that oxygen-glucose deprivation (OGD) also induced more GPR17 gene and protein expression than control at 48 h-72 h. There were more NG2+/GPR17+progenitor cells at 24 h-48 h and O4+/GPR17+precursor cells at 48 h-72 h in the OGD groups, as well. The functional role of GPR17 in the intrinsic repair response to ischemia was tested using GPR17 gene silencing. The progenitor cells and OL precursors in the OGD+GPR17 silencing group were both significantly less than those in the control, OGD and OGD+gene silencing control groups. The apoptotic percentage of cells in OGD+GPR17 silencing group was also much higher. In summary, ischemia-induced GPR17 expression was shown to contribute to glial-derived progenitor cell proliferation and differentiation into OL precursors, which may provide a therapeutic target for immature neonatal white matter injury after ischemia.

Effect of intravitreal ranibizumab pretreatment on vitrectomy in young patients with proliferative diabetic retinopathy.

BACKGROUND: Younger patients who underwent vitrectomy for proliferative diabetic retinopathy (PDR) display more aggressive nature distinguished from the older patients. Preoperative anti-VEGF therapy has been widely used as an adjunct for PDR surgery. However, the effect of anti-VEGF administration in young diabetics has rarely been evaluated in previous studies. The purpose of this study was to evaluate the effects of ranibizumab pretreatment on vitrectomy surgery in young patients with PDR. METHODS: This was a prospective nonrandomized comparative study. Young patients (<40 years old) undergoing diabetic vitrectomy with or without ranibizumab pretreatment (25 eyes in each group) were analyzed in this study. The use of the drug was determined by the patients' own preference. The two surgical groups were matched according to a complexity score. Intravitreal injection of ranibizumab (IVR) was performed 3-5 days prior to the vitrectomy surgery in the IVR group. Intraoperative records including total surgical time, intraoperative bleeding, the use of endodiathermy, the frequency of relaxing retinotomies, the incidence of iatrogenic retinal breaks, and the use of perfluorocarbon liquid (PFCL) and silicone oil tamponade, and postoperative indices regarding recurrent vitreous hemorrhage (VH), neovascular glaucoma (NVG), recurrent retinal detachment, and visual outcome were evaluated between the two groups. All patients were followed up for one year after surgery. RESULTS: In young PDR patients, the severity of intraoperative bleeding was significantly lower in the IVR group than in the control group (P=0.04). The total surgical time was shorter in the IVR group than in the control group. However, the rate of relaxing retinotomy, the incidence of iatrogenic retinal breaks and the use of PFCL and silicone oil tamponade were not affected by IVR pretreatment but affected by the complexity score of the case. Early postvitrectomy hemorrhage occurred less frequently in the IVR group than in the control group (P<0.001), Early visual recovery was better in the IVR group than in the control group (P=0.03). However, there were no significant differences in the development of late recurrent VH, NVG, recurrent retinal detachment, and final visual outcome. CONCLUSIONS: IVR pretreatment is a safe and effective adjunct to vitrectomy in reducing intraoperative and early postvitrectomy bleeding and should be suggested in young PDR patients. However, IVR does not reduce the incidence of intraoperative and late postoperative complications in these patients. The risk of iatrogenic retinal breaks and silicone oil use are closely correlated with the complexity score of the surgical cases.

CaSR is required for ischemia-induced proliferation and differentiation of white matter progenitor cells from neonatal rats.

This study was designed to investigate whether calcium-sensing receptor (CaSR) could induce immture white matter progenitor cells proliferation and differentiation into oligodendrocyte(OL) precursor cells after oxygen-glucose deprivation (OGD) in vitro. Progenitor cells of immature white matter originating from five-day-old newborn rats were divided into control, OGD, control + CaSR silencing, OGD + CaSR silencing, control + adenosine triphosphate magnesium chloride (ATP-MgCl2) and OGD + ATP-MgCl2 groups. Immunofluorescence, real-time RT-PCR, gene silencing, Hoechst 33342/propidium iodide (PI) and Flow cytometry tests were used to examine the proliferation, differentiation and survival of the white matter progenitor cells in the different treatment groups. The results showed that normal immature white matter progenitor cells have certain ability of self-proliferation and differentiation in vitro. OGD could further induce progenitor cells proliferation and differentiation into O4 + OL precursor cells by activating CaSR, but OGD also induced more necrosis and apoptosis of newborn cells and less MBP + OL formation. The addition of ATP-MgCl2 as an activating agent of CaSR further promoted cell proliferation and differentiation both under normal and OGD conditions and reduced OGD-induced apoptosis and necrosis, while CaSR silenced resulted in minimal cell proliferation, differentiation and survival. This study suggests that CaSR plays an important role in the induction of immature white matter progenitor cells proliferation and differentiation into OL precursor cells after OGD, which may provide a new angle to further study whether CaSR initiates the intrinsic repair potential of immature white matter after ischemia in vivo.

Change of Vascular Endothelial Growth Factor Levels following Vitrectomy in Eyes with Proliferative Diabetic Retinopathy.

PURPOSE: To study the change of concentrations of vascular endothelial growth factor (VEGF) in vitreous cavity after vitrectomy in eyes with proliferative diabetic retinopathy (PDR). METHODS: In this retrospective study, intravitreal fluid samples were taken at baseline (beginning of the vitrectomy) and postoperatively (several days later after vitrectomy) at the time of prophylactic injection of bevacizumab in forty-eight eyes of forty-eight patients with PDR. Postvitrectomy fluid samples were divided into four groups according to the time interval between the vitrectomy and the injection (group 1, 3-5 days; group 2, 6-10 days; group 3, 11-15 days; group 4, 16-21 days; twelve eyes in each group). Postvitrectomy fluid sample was paired with baseline sample for each eye. VEGF concentrations in the samples were determined by enzyme-linked immunosorbent assay. Recurrent vitreous hemorrhage and neovascular glaucoma within six months postvitrectomy were also analyzed. RESULTS: Overall, the intravitreal VEGF level after vitrectomy (median, 36.95 pg/ml; range, 3.2-1,299.4 pg/ml) was significantly less than the VEGF level at baseline (median, 704.5 pg/ml; range, 30.6-1,981.1 pg/ml). Postoperative and baseline VEGF levels were significantly correlated (r = 0.499, p < 0.01). Both the absolute value of postoperative VEGF concentrations and the postop/baseline VEGF ratios declined with time and dramatically decreased in groups 3 and 4. In only two eyes, the postoperative VEGF level was even higher than the baseline VEGF level (postop/baseline VEGF ratio >1), and recurrent vitreous hemorrhage developed within six months in these two eyes. CONCLUSIONS: After vitrectomy for PDR, intravitreal VEGF levels decreased substantially in the majority of patients, while persistent high-VEGF level occurred in a few individuals. Postoperative VEGF levels and postop/baseline VEGF ratio declined with time. The postop/preop VEGF ratio may serve as a predictor for late complications.

Traumatic macular hole study: a multicenter comparative study between immediate vitrectomy and six-month observation for spontaneous closure.

BACKGROUND: Closure of traumatic macular hole (TMH) can be achieved spontaneously or by surgical intervention. Thus far, there exist no prospective comparative studies that have analyzed the difference between the two modalities. This study aimed to compare the anatomical and visual recovery of eyes with TMH following either an immediate vitrectomy or six-month observation. METHODS: This was a multicenter prospective comparative study. Eight centers participated in the study. Patient data from 40 eyes with a recent history of blunt ocular trauma and newly formed full-thickness TMH were recruited in this study. The participating patients selected between an early vitrectomy or a six-month observation after a doctor explained the potential benefits and risks of both strategies in an unbiased manner. Twenty-five patients underwent an immediate vitrectomy, and 15 patients received six-month observation. Patients were assessed by spectral-domain optical coherence tomography (SD-OCT) and best-corrected visual acuity (BCVA). RESULTS: Closure rates were 66.7% for the observational group, and 100% for the surgical group (P=0.002). There were no vision-threatening ocular complications in both groups. For the observational group, the mean closure time was 2.5±1.6 months, and 80% of the hole closure occurred within 3 months; cystic edema on the edge of the hole at baseline was significantly more frequent in the non-closed subgroup than in the closed subgroup (P=0.03). There were no significant differences in the foveal microstructure and in the final visual outcome between the spontaneously closed cases and the surgically closed cases. CONCLUSIONS: TMH had a moderately high incidence of spontaneous closure, but an immediate vitrectomy achieved an even higher closure rate. Vitrectomy was effective and safe to treat TMH, while a 3-month observation for spontaneous closure may be an alternative modality for TMH management. Cystic edema on the edge of the hole may be an unfavorable factor for the spontaneous closure of TMH.

Postiridotomy ultrasound biomicroscopy features in the fellow eye of Chinese patients with acute primary angle-closure and chronic primary angle-closure glaucoma.

PURPOSE: To compare the features of postiridotomy ultrasound biomicroscopy (UBM) in Chinese patients with acute primary angle-closure (aPAC) and with chronic primary angle-closure (cPAC) glaucoma. PATIENTS AND METHODS: Consecutive cases were classified into acute and chronic groups. The acute group included 77 patients with unilateral aPAC. The chronic group included 57 patients with unilateral advanced cPAC glaucoma. In both the groups, the patients' fellow eye underwent a laser iridotomy and was studied. The main outcome measures included qualitative UBM parameters such as a plateau iris, anterior iris insertion, and an anteriorly rotated ciliary process and quantitative UBM parameters such as central anterior chamber depth (ACD), basal iris thickness (IT500), and scleral ciliary process angle (SCPA). RESULTS: For the qualitative parameters, more eyes in the chronic group had a plateau iris (P=0.046), an anterior iris insertion (P=0.222), and an anteriorly rotated ciliary process (P=0.090) than those in the acute group. For the quantitative parameters, the eyes in the chronic group had a deeper ACD (P<0.001), thicker IT500 (P<0.001), and smaller SCPA (P<0.001) than those in the acute group. CONCLUSIONS: The UBM features of Chinese patients with cPAC include a more plateaued iris, a thicker basal iris, and a smaller SCPA, whereas patients with aPAC may have a shallower ACD. For Chinese patients, a nonpupillary block component may play a more important role in asymptomatic cPAC than in aPAC.

Anatomical outcome of vitreoretinal surgery using temporary keratoprosthesis and replacement of the trephined corneal button for severe open globe injuries: one-year result.

In this case series of 74 patients with coexisting vitreoretinal injury and severe corneal opacification, after temporary keratoprosthesis (TKP) assisted pars plana vitrectomy (PPV), an allograft corneal transplant was not performed at the same time; instead, the patient's trephined corneal button was sutured back. One year after the surgery, if intraocular pressure of the injured eyes was above 8 mmHg, removing silicone oil was attempted, and penetrating keratoplasty could be performed. Finally, 10 eyes (13.5%) were enucleated due to atrophia bulbi; 46 eyes (62.2%) were silicone-oil sustained; 15 eyes (20.3%) were anatomically restored; and 3 eyes (4.0%) experienced recurrent retinal detachment. These figures only demonstrate a small percentage of the injured eyes in our series, which have PKP indications. It is a practical option to suture back the patient's trephined cornea following a TKP assisted PPV; keratoplasty was reserved for selected cases.

White matter and SVZ serve as endogenous sources of glial progenitor cells for self-repair in neonatal rats with ischemic PVL.

Mounting evidence suggests that endogenous progenitor cells may initiate cerebral WM repair. This study was designed to determine whether endogenous glial progenitor cells derived from either the subventricular zone (SVZ) or the white matter (WM) contribute to WM repair in a neonatal rat model of ischemic periventricular leukomalacia (PVL). Additionally, the role of G protein-coupled receptor 17 (GPR17), recently shown to act as a sensor for WM damage, was explored to assess its potential recruitment and activation of endogenous glial progenitor cells for such WM self-repair. Our in vivo and in vitro models consisted of five-day-old neonatal rats or cultured glial progenitor cells derived from both the SVZ and WM of these rats, randomly divided into sham/control and induced ischemic PVL/oxygen-glucose deprivation (OGD) groups. The WM of all PVL rats showed either mild or severe histopathological changes, with significantly increased in vivo apoptosis and poor myelination compared to those of the sham group. Significantly more apoptotic and necrotic cells were also detected in the OGD glial progenitor cell cultures derived from the SVZ and WM at all time intervals. The glial progenitor cells were significantly increased in both the SVZ (NG2⁺/GPR17⁻/BrdU⁺) and WM (NG2⁺/GPR17⁺/BrdU⁺) within 72 h after PVL; preOLs were also increased significantly in both the SVZ (O4⁺/GPR17⁻/BrdU⁺) and WM (O4⁺/GPR17⁺/BrdU⁺) within 7d after PVL in vivo or OGD in vitro. However, the more differentiated CNPase⁺/GPR17⁻/BrdU⁺ and MBP⁺/GPR17⁻/BrdU⁺ OLs in the SVZ and WM remained significantly less than those in the sham groups up to 14d or 21d after OGD or PVL, respectively. Hence, both the WM and SVZ were found to be potential endogenous sources of glial progenitor cells for WM repair in PVL rats. However their endogenous self-repair capacity appeared to be limited, since the more mature OLs did not completely recover from experimental ischemia, even after 14-21d.

Incidence of brain injuries in premature infants with gestational age ≤ 34 weeks in ten urban hospitals in China.

BACKGROUND: There is a large number (1.5 million per year) of premature births in China. It is necessary to obtain the authentic incidences of intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL), the common brain injuries, in Chinese premature infants. The present multicenter study aimed to investigate the incidence of brain injuries in premature infants in ten urban hospitals in China. METHODS: The research proposal was designed by the Subspecialty Group of Neonatology of Pediatric Society of the Chinese Medical Association. Ten large-scale urban hospitals voluntarily joined the multicenter investigation. All premature infants with a gestational age ≤ 34 weeks in the ten hospitals were subjected to routine cranial ultrasound within three days after birth, and then to repeated ultrasound every 3-7 days till their discharge from the hospital from January 2005 to August 2006. A uniform data collection sheet was designed to record cases of brain injuries. RESULTS: The incidences of overall IVH and severe IVH were 19.7% (305/1551) and 4.6% (72/1551), respectively with 18.4% (56/305) for grade 1, 58.0% (177/305) for grade 2, 17.7% (54/305) for grade 3 and 5.9% (18/305) for grade 4 in nine hospitals. The incidences of overall PVL and cystic PVL were 5.0% (89/1792) and 0.8% (14/1792) respectively, with 84.3% (75/89) for grade 1, 13.5% (12/89) for grade 2, and 2.2% (2/89) for grade 3 in the ten hospitals. The statistically significant risk factors that might aggravate the severity of IVH were vaginal delivery (OR=1.883, 95% CI: 1.099-3.228, P=0.020) and mechanical ventilation (OR=4.150, 95% CI: 2.384-7.223, P=0.000). The risk factors that might result in the development of cystic PVL was vaginal delivery (OR=21.094, 95% CI: 2.650-167.895, P=0.000). CONCLUSIONS: The investigative report can basically reflect the incidence of brain injuries in premature infants in major big cities of China. Since more than 60% of the Chinese population live in the rural areas of China, it is expected to undertake a further multicenter investigation covering the rural areas in the future.

Diphenyleneiodonium protects preoligodendrocytes against endotoxin-activated microglial NADPH oxidase-generated peroxynitrite in a neonatal rat model of periventricular leukomalacia.

The contribution of microglial activation to preoligodendroglial (preOL) damage in the central nervous system (CNS) is considered to be one of the principal causes of periventricular leukomalacia (PVL) pathogenesis. The present study explores the effect of diphenyleneiodonium (DPI), a NADPH oxidase (NOX) inhibitor, on protection of preOLs from bacterial lipopolysaccharide (LPS)-induced microglial toxicity in vivo and in vitro. In vitro, preOLs co-cultured with microglia exhibited increased preOL apoptosis, accompanied by overproduction of superoxide anion (O(2)(-)) and the formation of peroxynitrite (ONOO(-)) after LPS exposure. LPS also significantly up-regulated accumulation of activated microglial NOX subunits p67-phox and gp91-phox in the plasma membrane. Diphenyleneiodonium (DPI) (10µm) was found to significantly attenuate up-regulation of this NOX activity. In vivo, DPI was administered (1mg/kg/day) by subcutaneous injection for 3 days to two-day-old neonatal Sprague-Dawley rats subjected to intracerebral injection of LPS. Treatment with DPI within 24h of LPS injection significantly ameliorated white matter injury, decreasing preOL loss, O(2)(-) generation, and ONOO(-) formation, and inhibiting p67-phox, gp91-phox synthesis and p67phox membrane translocation in microglia. These results indicated that LPS-induced preOL apoptosis may have been mediated by microglia-derived ONOO(-). DPI prevented this LPS-induced brain injury, most likely by inhibiting ONOO(-) formation via NOX, thereby preventing preOL loss and immature white matter injury.

[Effect of single or combined application of UDP-glucose, GDNF and memantine on improvement of white matter injury in neonatal rats assessed with light and electron microscopy pathologically].

OBJECTIVE: To evaluate pathologically the effect of the single or combined application of UDP-glucose, GDNF and memantine on the improvement of white matter injury in neonatal rats with periventricular leukomalacia (PVL) under light and electron microscopy. METHODS: A five-day-old neonatal rat model for PVL was established by ligation of the lateral common carotid artery following 120-minute hypoxia. Rats were randomly divided into six groups (30 rats in each group): sham-operated, PVL, UDP-glucose (UDP-glucose 2000 mg/kg intraperitoneally after PVL), GDNF (GDNF 100 µg/kg intracerebrally after PVL), tmemantine (memantine 20 mg/kg intraperitoneally after PVL), and a combination administration of three drugs (UDP-glucose, GDNF and memantine). The rats were sacrificed 7 or 21 days after PVL for assessment of pathological changes in the white matter under both light and electron microscopy. The number and thickness of the myelin sheath in the white matter were measured under electron microscopy, and both of pathological grading and scoring were undertaken under light microscopy. RESULTS: There was rare and sparse myelinogenesis with a loose arrangement of nerve fibers in the white matter under electron microscopy in the PVL group at 7 and 21 days after PVL. The number and thickness of the myelin sheath in the PVL group were significantly less than in the sham-operated, UDP-glucose, GDNF, memantine and combination administration groups (P<0.01). The results of pathological grading of white matter under light microscopy showed that all rats in the PVL group manifested either mild injury (38%-50%) or severe injury (50%-62%) at 7 and 21 days after PVL. The majority of rats (50%-88%) in the four drug administration groups had normal white matter at 7 and 21 days after PVL. The pathological scores at 7 and 21 days after PVL in the PVL group were the highest, and they were significantly higher than in the other five groups (P<0.05). CONCLUSIONS: The single or combined application of UDP-glucose, GDNF and memantine may significantly improve pathological changes in the white matter of rats with PVL. The favorable effect is inferred to be closely correlated with the improvement of brain microenvironment and the enhancement of nerve regeneration promoted by the three drugs.

Periventricular leukomalacia long-term prognosis may be improved by treatment with UDP-glucose, GDNF, and memantine in neonatal rats.

The therapeutic effects of UDP-glucose (UDPG), an endogenous agonist of GPR17 that may promote the self-repair of white matter, glial cell line-derived neurotrophic factor (GDNF), a neurotrophic factor correlated with the growth and survival of nerve cells, and memantine, an antagonist of NMDA receptors, were evaluated for functional improvement of neonatal rats with experimental periventricular leukomalacia (PVL). Five day-old neonatal rat pups were subjected to an ischemia-induced model of PVL. The pups were then randomly divided into sham, PVL, PVL plus UDPG, PVL plus GDNF, and PVL plus memantine groups. All pups were weighed and the age at first eye opening recorded. Pathological changes and myelin sheath formation in the white matter were assessed under both light and electron microscopy on day 7 and 21 after induction of PVL. Values of escape latency (EL) and swimming distance (SD) in Morris water maze test, and the modified inclined plane scores in Rivlin inclined plane test were recorded for rats on day 26. Pups in the PVL group were found to be significantly lower in weight (p<0.05), delayed in age at first eye opening (p<0.01), and impaired in their inclined plane (p<0.01) and Morris water maze (p<0.01) performance compared with those in the sham, UDPG, GDNF and memantine groups. Histopathological grading of the white matter classified all pups in the PVL group with significantly more severe injury (p<0.01), and the number and thickness of their myelin sheaths were significantly less (p<0.01), compared to the UDPG, GDNF, memantine, or sham groups. These results indicate that treatment with UDPG, GDNF, and memantine may significantly improve long-term prognosis in neonatal rats with cerebral white matter injury, characteristic of PVL.

[Endogenous self-repair in immature white matter induced by ischemia in neonatal rats].

OBJECTIVE: To study in vivo the endogenous self-repair mechanism in immature white matter induced by ischemia in neonatal rats with periventricular leukomalacia (PVL). METHODS: Five-day-old neonatal Sprague-Dawley (SD) rats were randomly divided into sham and PVL groups. Rat model of PVL was prepared by ligation of the right common carotid artery following 2 hours of exposure to 8% oxygen. Pathological changes and myelination in the white matter were assessed under light and electron microscopy at 7 and 21 days after PVL. O4-positive OL precursor cells in the white matter were determined with immunofluorescence staining. Activation, proliferation, migration and differentiation of glial progenitor cells in SVZ were observed using immunofluorescent double labeling of either NG2 (marker of progenitor cells) and 5-bromodeoxyuridine (BrdU), or O4 (marker of OL precursor cells) and BrdU. RESULTS: All rats in the PVL group manifested either mild or severe white matter injury under light microscopy, and had higher pathological scores of white matter compared with the sham group at 7 and 21 days after PVL (P<0.05). Electron microscopy showed that the number and thickness of myelin sheath in the PVL group were significantly reduced compared with the sham group (P<0.01). O4-positive OL precursor cells in the white matter observed under fluorescence microscopy were significantly reduced in the PVL group compared with the sham group (P<0.05). BrdU/NG2-positive cells in the SVZ increased significantly in the PVL group 48 hours after PVL and migrated into the periventricular area, reaching a peak on day 7 after PVL. BrdU/O4-positive newborn cells began to appear in the periventricular area 72 hours after PVL, and the number of BrdU/O4-positive cells in the PVL group was statistically more than in the sham group on day 21 after PVL (P<0.05). CONCLUSIONS: Ischemia may induce brain self-repair in neonatal rats, resulting in activation and proliferation of NG2 glial progenitor cells in the SVZ migration and differentiation into OL precursor cells in periventricular white matter.

[Effects of glial cell line-derived neurotrophic factor and memantine on long-term prognosis in neonatal rats with periventricular leukomalacia].

OBJECTIVE: To evaluate the effects of glial cell line-derived neurotrophic factor (GDNF) and memantine on the long-term prognosis in neonatal rats with ischemia-induced periventricular leukomalacia (PVL). METHODS: Thirty-two 5-day-old neonatal rats were randomly divided into 4 groups: sham-operated, PVL, GDNF-treated and memantine-treated. PVL was induced by right carotid artery ligation and hypoxia in the PVL, GDNF-treated and memantine-treated groups. GDNF (100 µg/kg) or memantine (20 mg/kg) was injected in the two treatment groups immediately after PVL inducement. The weight of the rats was measured immediately before and after hypoxia ischemia (HI). Both of Morris water maze test and Rivlin inclined plane test were performed at 26 days old (21 days after HI). The values of the escape latency (EL) and swimming distance, and the maximum inclined plane degree which the rats could stand at least 5 seconds were compared among the four groups. RESULTS: The lower weight, the prolonged mean values of EL and swimming distance and the reduced maximum inclined plane degree were observed in the PVL group compared to those in the sham-operated, GDNF-treated and memantine-treated groups. There were no significant differences in the weight, the values of EI and swimming distance and the maximum inclined plane degree between the two treatment groups and the sham-operated group. CONCLUSIONS: The administration of either GDNF or memantine can markedly increase the abilities of spatial discrimination,learning and memory, and motor coordination, promote weight gain, and improve long-term prognosis in rats with PVL.