Genetic characterization of cucumber genetic resources in the NARO Genebank indicates their multiple dispersal trajectories to the East.

KEY MESSAGE: Genotyping-by-sequencing of 723 worldwide cucumber genetic resources revealed that cucumbers were dispersed eastward via at least three distinct routes, one to Southeast Asia and two from different directions to East Asia. The cucumber (Cucumis sativus) is an economically important vegetable crop cultivated and consumed worldwide. Despite its popularity, the manner in which cucumbers were dispersed from their origin in South Asia to the rest of the world, particularly to the east, remains a mystery due to the lack of written records. In this study, we performed genotyping-by-sequencing (GBS) on 723 worldwide cucumber accessions, mainly deposited in the Japanese National Agriculture and Food Research Organization (NARO) Genebank, to characterize their genetic diversity, relationships, and population structure. Analyses based on over 60,000 genome-wide single-nucleotide polymorphisms identified by GBS revealed clear genetic differentiation between Southeast and East Asian populations, suggesting that they reached their respective region independently, not progressively. A deeper investigation of the East Asian population identified two subpopulations with different fruit characteristics, supporting the traditional classification of East Asian cucumbers into two types thought to have been introduced by independent routes. Finally, we developed a core collection of 100 accessions representing at least 93.2% of the genetic diversity present in the entire collection. The genetic relationships and population structure, their associations with geographic distribution and phenotypic traits, and the core collection presented in this study are valuable resources for elucidating the dispersal history and promoting the efficient use and management of genetic resources for research and breeding in cucumber.

Melon diversity on the Silk Road by molecular phylogenetic analysis in Kazakhstan melons.

To uncover population structure, phylogenetic relationship, and diversity in melons along the famous Silk Road, a seed size measurement and a phylogenetic analysis using five chloroplast genome markers, 17 RAPD markers and 11 SSR markers were conducted for 87 Kazakh melon accessions with reference accessions. Kazakh melon accessions had large seed with exception of two accessions of weedy melon, Group Agrestis, and consisted of three cytoplasm types, of which Ib-1/-2 and Ib-3 were dominant in Kazakhstan and nearby areas such as northwestern China, Central Asia and Russia. Molecular phylogeny showed that two unique genetic groups, STIa-2 with Ib-1/-2 cytoplasm and STIa-1 with Ib-3 cytoplasm, and one admixed group, STIAD combined with STIa and STIb, were prevalent across all Kazakh melon groups. STIAD melons that phylogenetically overlapped with STIa-1 and STIa-2 melons were frequent in the eastern Silk Road region, including Kazakhstan. Evidently, a small population contributed to melon development and variation in the eastern Silk Road. Conscious preservation of fruit traits specific to Kazakh melon groups is thought to play a role in the conservation of Kazakh melon genetic variation during melon production, where hybrid progenies were generated through open pollination.

Elucidation of genetic variation and population structure of melon genetic resources in the NARO Genebank, and construction of the World Melon Core Collection.

Numerous genetic resources of major crops have been introduced from around the world and deposited in Japanese National Agriculture and Food Research Organization (NARO) Genebank. Understanding their genetic variation and selecting a representative subset ("core collection") are essential for optimal management and efficient use of genetic resources. In this study, we conducted genotyping-by-sequencing (GBS) to characterize the genetic relationships and population structure in 755 accessions of melon genetic resources. The GBS identified 39,324 single-nucleotide polymorphisms (SNPs) that are distributed throughout the melon genome with high density (one SNP/10.6 kb). The phylogenetic relationships and population structure inferred using this SNP dataset are highly associated with the cytoplasm type and geographical origin. Our results strongly support the recent hypothesis that cultivated melon was established in Africa and India through multiple independent domestication events. Finally, we constructed a World Melon Core Collection that covers at least 82% of the genetic diversity and has a wide range of geographical origins and fruit morphology. The genome-wide SNP dataset, phylogenetic relationships, population structure, and the core collection provided in this study should largely contribute to genetic research, breeding, and genetic resource preservation in melon.

Contrast-enhanced CT features of pyloric lesions in 17 dogs: Case series.

Pyloric outflow obstructions can be caused by several types of lesions. When a thickened gastric wall and pyloric mass are detected, malignant neoplasia must be differentiated from chronic hypertrophic pyloric gastropathy. CT can characterize gastric tumors. However, based on the authors' review of the literature, there is limited information about the CT findings of pyloric lesions. The purpose of this retrospective case series study was to assess the CT findings of canine pyloric lesions. The following CT parameters were recorded: anatomical area, involved area, lesion shape, growth patterns of wall thickening lesions, enhancement pattern of the lesion in the early and delayed phases, lymphomegaly, and pulmonary metastasis. Seventeen dogs were included in this study and had the following final diagnoses: hyperplasia (five dogs), adenoma (five dogs), adenocarcinoma (three dogs), gastrointestinal stromal tumor (GIST; two dogs), polyposis (one dog), and pyogenic granuloma (one dog). Hyperplasia, adenoma, and polyposis formed mass lesions that involved the mucosal layer. Lymphomegaly was detected in two Jack Russell terriers with hyperplasia; however, the causes were unknown because we did not perform biopsies. All adenocarcinomas formed wall-thickened lesion that involved the outer layer, with lymphomegaly. All GISTs formed mass lesion that involved the outer layer. The pyogenic granulomas formed symmetric wall-thickened lesion that involved the mucosal and outer layers. CT facilitated the characterization of canine pyloric lesions using contrast enhancement, based on the involved area and lesion shape. However, polyposis may require caution in diagnosis based on CT findings alone.

Distribution of two groups of melon landraces and inter-group hybridization enhanced genetic diversity in Vietnam.

To understand the genetic diversity and differentiation of Vietnamese melon (Cucumis melo L.), we collected 64 landraces from the central and southern parts of the country and assessed molecular polymorphism using simple sequence repeat and random amplified polymorphic DNA markers. The Vietnamese melon was divided into seven cultivar groups, namely "Dua le", "Dua vang", "Dua bo", "Dua gang-andromonoecious", "Dua gang-monoecious", "Dua thom", "Montok", and the weedy-type melon "Dua dai". Among these, Dua le, Dua vang, Dua bo, and Dua gang-andromonoecious are cultivated on plains and they formed cluster II along with the reference accessions of Conomon and Makuwa. Based on genetic distance, Dua le and Dua vang were regarded as Makuwa and Dua bo and Dua gang-andromonoecious as Conomon. In contrast, Dua thom and Montok are cultivated in highlands, and they formed cluster III along with landraces from the southern and eastern foot of the Himalayas. Dua gang-monoecious which is commonly cultivated in the southern parts of Vietnam, exhibited the greatest genetic diversity, as explained by its possible origin through the hybridization between Dua gang-andromonoecious and Montok. Genetic differences in melon landraces between plains and highlands and hybridization between these two geographical groups have contributed to the enhancement of genetic diversity in Vietnamese melon.

Plasma microRNA miR-26b as a potential diagnostic biomarker of degenerative myelopathy in Pembroke welsh corgis.

BACKGROUND: Degenerative myelopathy (DM) is a progressive neurodegenerative disease frequently found in Pembroke Welsh Corgis (PWCs). Most DM-affected PWCs are homozygous for the mutant superoxide dismutase 1 (SOD1) allele; however, the genetic examination for the SOD1 mutation does not exclusively detect symptomatic dogs. In order to identify novel biomarkers, the plasma microRNA (miRNA) profiles of PWCs with DM were investigated. RESULTS: Quantification of the plasma levels of 277 miRNAs by an RT-qPCR array identified 11 up-regulated miRNAs and 7 down-regulated miRNAs in DM-affected PWCs from those in wild-type SOD1 PWCs. A pathway analysis identified 3 miRNAs: miR-26b, miR-181a, and miR-196a, which potentially regulate several genes associated with SOD1. In order to validate the diagnostic accuracy of the candidate miRNAs in the aged PWC population, candidate miRNAs in plasma were measured by RT-qPCR and a receiver operating characteristic (ROC) curve analysis was performed. miR-26b had the largest area under the ROC curve for distinguishing DM PWCs from healthy PWCs (sensitivity, 66.7%; specificity, 87.0%). The plasma level of miR-26b was significantly higher in the DM group than in the healthy control group. A positive correlation was observed between increases in the plasma level of miR-26b and disease progression. CONCLUSIONS: These results suggest that plasma miR-26b is a potential novel diagnostic biomarker of DM.

Chromatographically isolated CD63+CD81+ extracellular vesicles from mesenchymal stromal cells rescue cognitive impairments after TBI.

Extracellular vesicles (EVs) secreted by cells present an attractive strategy for developing new therapies, but progress in the field is limited by several issues: The quality of the EVs varies with the type and physiological status of the producer cells; protocols used to isolate the EVs are difficult to scale up; and assays for efficacy are difficult to develop. In the present report, we have addressed these issues by using human mesenchymal stem/stromal cells (MSCs) that produce EVs when incubated in a protein-free medium, preselecting the preparations of MSCs with a biomarker for their potency in modulating inflammation, incubating the cells in a chemically defined protein-free medium that provided a stable environment, isolating the EVs with a scalable chromatographic procedure, and developing an in vivo assay for efficacy of the cells in suppressing neuroinflammation after traumatic brain injury (TBI) in mice. In addition, we demonstrate that i.v. infusion of the isolated EVs shortly after induction of TBI rescued pattern separation and spatial learning impairments 1 mo later.

A novel patient-specific drill guide template for stabilization of thoracolumbar vertebrae of dogs: cadaveric study and clinical cases.

OBJECTIVE: To evaluate the accuracy and safety of a novel patient-specific drill guide template for stabilizing the thoracolumbar vertebrae of dogs. STUDY DESIGN: Cadaveric experimental study and prospective case series. SAMPLE POPULATION: Cadaveric canine thoracolumbar vertebral specimens (n = 3) and clinical cases of thoracolumbar spinal instability (n = 4). METHODS: Computed tomography data of the thoracolumbar spines were obtained before surgery, and images were imported into imaging software. Optimum screw trajectories were selected for each vertebra, and drill guide templates were designed and fabricated with a 3-dimensional printing system. Drill guide templates were applied to cadaveric spine and clinical cases. Computed tomography imaging was performed after surgery, and planned and postoperative trajectories were compared to estimate the accuracy and safety of the drill guide templates. RESULTS: Twenty-two drill holes were made in cadaveric spinal specimens. All drill holes were completely located in the bone. The overall mean screw deviation was 0.88 ± 0.36 mm. In clinical cases, 29 screws were placed in thoracolumbar vertebrae. Most (89.6%) of these screws were placed without evidence of vertebral canal invasion. One (3.5%) screw perforated the bone structure. The overall mean screw deviation was 1.16 ± 0.56 mm. CONCLUSION: Drill guide templates were useful for accurate intraoperative screw navigation in thoracolumbar fixation in small dogs. CLINICAL SIGNIFICANCE: The use of drill guide templates can be considered as an aid to safety and accuracy of screw placement in canine thoracolumbar instabilities.

Expression of IL-33 in chronic lesional skin of canine atopic dermatitis.

BACKGROUND: In humans, interleukin (IL)-33 plays a critical role in the enhancement of allergic skin inflammation. However, it currently remains unclear whether IL-33 is involved in the pathogenesis of canine atopic dermatitis (cAD). OBJECTIVES: To examine the expression of IL-33 in chronic lesional skin of cAD. ANIMALS: Eight dogs with spontaneous cAD and five healthy dogs were used. METHODS: The transcription of il-33 in chronic lesional skin of cAD was quantified by quantitative reverse transcription PCR. The expression of IL-33 was evaluated immunohistochemically using an anti-human IL-33 monoclonal antibody with cross-reactivity to canine IL-33. RESULTS: The transcription levels of il-33 in chronic lesional skin of cAD were significantly higher than those in normal skin of healthy dogs. Keratinocytes were a major cellular source of IL-33 production in chronic lesional skin of cAD. CONCLUSIONS AND CLINICAL IMPORTANCE: The results indicate that IL-33 is involved in chronic lesional skin of cAD.

Expression of ZO-1 and claudin-1 in a 3D epidermal equivalent using canine progenitor epidermal keratinocytes.

BACKGROUND: Previous studies indicate that tight junctions are involved in the pathogenesis of canine atopic dermatitis (cAD). An in vitro skin model is needed to elucidate the specific role of tight junctions in cAD. A 3D epidermal equivalent model using canine progenitor epidermal keratinocytes (CPEK) has been established; the expression of tight junctions within this model is uncharacterized. HYPOTHESIS/OBJECTIVES: To investigate the expression of tight junctions in the 3D epidermal equivalent. ANIMALS: Two normal laboratory beagle dogs served as donors of full-thickness skin biopsy samples for comparison to the in vitro model. METHODS: Immunohistochemical techniques were employed to investigate the expression of tight junctions including zonula occludens (ZO)-1 and claudin-1 in normal canine skin, and in the CPEK 3D epidermal equivalent. RESULTS: Results demonstrated the expression of ZO-1 and claudin-1 in the CPEK 3D epidermal equivalent, with staining patterns that were similar to those in normal canine skin. CONCLUSIONS AND CLINICAL IMPORTANCE: The CPEK 3D epidermal equivalent has the potential to be a suitable in vitro research tool for clarifying the specific role of tight junctions in cAD.

Transcriptional analysis of the IL-33 receptor suppression of tumourigenicity 2 and its effects on canine Type 2 T helper cells: a preliminary study.

BACKGROUND: Interleukin (IL)-33 has been implicated in the pathogenesis of canine atopic dermatitis, a Type 2 T helper cell (Th2)-associated disease. In humans, IL-33 mediates its biological effects through the receptor suppression of tumourigenicity 2 (ST2), which is preferentially expressed on Th2 cells. The effects of IL-33 on canine Th2 cells are unclear. HYPOTHESIS/OBJECTIVES: ST2 may be preferentially expressed on canine Th2 cells; IL-33 may induce the transcription of Th2 cytokines from these cells. ANIMALS: Three healthy dogs were used. METHODS: The transcription level of st2 was quantified in helper T cells, cytotoxic T cells and Th2 cells isolated from healthy dogs. The transcription levels of Th2 cytokines including il-4, il-5, il-13 and il-31 were quantified in Th2 cells stimulated with recombinant canine (rc) IL-33 and/or recombinant human (rh) IL-2. RESULTS: Transcription of st2 was the strongest in Th2 cells. Th2 cells also transcribed the genes for il-5 and il-13 after being stimulated with rcIL-33 and rhIL-2. CONCLUSIONS AND CLINICAL IMPORTANCE: These results indicate that canine Th2 cells activated by IL-33 enhance Th2-mediated inflammation through the production of IL-5 and IL-13.

Phenotypic analysis of mice xenografted with canine epitheliotropic cutaneous T-cell lymphoma cells.

BACKGROUND: In canine epitheliotropic cutaneous T-cell lymphoma (ECTCL), neoplastic cells cause skin lesions and potentially metastasize to lymph nodes, blood and other organs. Murine models are potentially valuable for elucidating the molecular mechanisms responsible for regulation of ECTCL cell migration. HYPOTHESIS/OBJECTIVES: To describe a phenotype of mice xenografted with canine ECTCL cells (EO-1 cells). ANIMALS: Four NOD.CB17-Prkdcscid /J (NOD SCID) mice were used. METHODS AND MATERIALS: EO-1 cells were subcutaneously xenografted into NOD SCID mice. After four weeks, the development of tumour lesions in skin and other organs was investigated. RESULTS: Mice developed skin lesions with metastasis to the lymph nodes, spleen, lung, blood and liver. CONCLUSIONS AND CLINICAL IMPORTANCE: Mice xenografted with EO-1 cells may be useful for studying the pathogenesis of canine ECTCL.

Fluorescein sodium-guided resection of intracranial lesions in 22 dogs.

OBJECTIVE: To evaluate the safety of an intraoperative fluorescein sodium (FS) injection and elucidate the relationships between the MRI findings, pathological diagnoses, and intraoperative staining characteristics of intracranial lesions in 22 dogs. STUDY DESIGN: Prospective case series. ANIMALS: Twenty-two dogs with intracranial lesions. METHODS: FS was intravenously administered to 22 dogs undergoing craniotomy for suspected intracranial tumors to evaluate perioperative and postoperative adverse effects. The intensities and patterns of gadolinium (Gd) enhancement on preoperative magnetic resonance imaging and intraoperative FS staining were graded, and their relationship was evaluated. Intraoperative FS staining characteristics and pathological diagnoses were compared. RESULTS: The only adverse effect noted was repetitive vomiting in 2 dogs. The intensities and patterns between preoperative Gd enhancement and intraoperative FS staining appeared to agree. High-grade glioma and histiocytic sarcoma had more intense FS staining. Lesions with strong Gd enhancement, including meningiomas and choroid plexus tumors, also had intense FS staining. CONCLUSION: The intraoperative use of FS is a simple and safe technique to guide the resection of intracranial lesions in dogs. The findings on Gd enhancement, FS staining, and histopathology appeared to agree but require validation in a larger set of cases. CLINICAL SIGNIFICANCE: The intraoperative use of FS may improve the prognosis of dogs with brain tumors by guiding the resection of lesions.

Methylprednisolone sodium succinate reduces spinal cord swelling but does not affect recovery of dogs with surgically treated thoracolumbar intervertebral disk herniation.

The effect of methylprednisolone sodium succinate (MPSS) therapy was studied in 50 dogs with surgically treated Hansen type I thoracolumbar intervertebral disk herniation (TL-IVDH). Administration of MPSS significantly reduced the swelling of the spinal cord. The sensitivity of localization of disk extrusion using myelography in the MPSS group was 92.3%, and in the non-administration group was 83.3%. No significant difference in recovery rate or length of recovery time was found between the two groups. Administration of MPSS reduced spinal cord swelling, but has no effect on recovery in dogs after surgery for TL-IVDH.

Fine mapping and epistatic interactions of the vernalization gene VRN-D4 in hexaploid wheat.

Wheat vernalization requirement is mainly controlled by the VRN1, VRN2, VRN3, and VRN4 genes. The first three have been cloned and have homoeologs in all three genomes. VRN4 has been found only in the D genome (VRN-D4) and has not been cloned. We constructed a high-density genetic map of the VRN-D4 region and mapped VRN-D4 within a 0.09 cM interval in the centromeric region of chromosome 5D. Using telocentric 5D chromosomes generated from the VRN-D4 donor Triple Dirk F, we determined that VRN-D4 is located on the short arm. The VRN-D4 candidate region is colinear with a 2.24 Mb region on Brachypodium distachyon chromosome 4, which includes 127 predicted genes. Ten of these genes have predicted roles in development but we detected no functional polymorphisms associated to VRN-D4. Two recombination events separated VRN-D4 from TaVIL-D1, the wheat homolog of Arabidopsis vernalization gene VIL1, confirming that this gene is not a candidate for VRN-D4. We detected significant interactions between VRN-D4 and other four genes controlling vernalization requirement (Vrn-A1, Vrn-B1, Vrn-D1, and Vrn-B3), which confirmed that VRN-D4 is part of the vernalization pathway and that it is either upstream or is part of the regulatory feedback loop involving VRN1, VRN2 and VRN3 genes. The precise mapping of VRN-D4 and the characterization of its interactions with other vernalization genes provide valuable information for the utilization of VRN-D4 in wheat improvement and for our current efforts to clone this vernalization gene.

Phytochrome C is a key factor controlling long-day flowering in barley.

The spring-type near isogenic line (NIL) of the winter-type barley (Hordeum vulgare ssp. vulgare) var. Hayakiso 2 (HK2) was developed by introducing VERNALIZATION-H1 (Vrn-H1) for spring growth habit from the spring-type var. Indo Omugi. Contrary to expectations, the spring-type NIL flowered later than winter-type HK2. This phenotypic difference was controlled by a single gene, which cosegregated only with phytochrome C (HvPhyC) among three candidates around the Vrn-H1 region (Vrn-H1, HvPhyC, and CASEIN KINASE IIα), indicating that HvPhyC was the most likely candidate gene. Compared with the late-flowering allele HvPhyC-l from the NIL, the early-flowering allele HvPhyC-e from HK2 had a single nucleotide polymorphism T1139C in exon 1, which caused a nonsynonymous amino acid substitution of phenylalanine at position 380 by serine in the functionally essential GAF (3', 5'-cyclic-GMP phosphodiesterase, adenylate cyclase, formate hydrogen lyase activator protein) domain. Functional assay using a rice (Oryza sativa) phyA phyC double mutant line showed that both of the HvPhyC alleles are functional, but HvPhyC-e may have a hyperfunction. Expression analysis using NILs carrying HvPhyC-e and HvPhyC-l (NIL [HvPhyC-e] and NIL [HvPhyC-l], respectively) showed that HvPhyC-e up-regulated only the flowering promoter FLOWERING LOCUS T1 by bypassing the circadian clock genes and flowering integrator CONSTANS1 under a long photoperiod. Consistent with the up-regulation, NIL (HvPhyC-e) flowered earlier than NIL (HvPhyC-l) under long photoperiods. These results implied that HvPhyC is a key factor to control long-day flowering directly.

Evaluation of serum phosphorylated neurofilament subunit NF-H as a prognostic biomarker in dogs with thoracolumbar intervertebral disc herniation.

OBJECTIVE: To investigate whether pNF-H is a prognostic biomarker of spinal cord injury (SCI) in paraplegic dogs with thoracolumbar intervertebral disc herniation (IVDH). STUDY DESIGN: Prospective, case-control clinical study ANIMALS: Dogs (n = 60) with SCI from IVDH and 6 healthy dogs. METHODS: Serum from 60 thoracolumbar IVDH dogs (Grade 4: 22 dogs; Grade 5: 38 dogs) collected 1-3 days after injury, and 6 control dogs, was analyzed using enzyme-linked immunosorbent assay (ELISA) against a phosphorylated form of the high-molecular-weight neurofilament subunit NF-H (pNF-H). Serum pNF-H levels were compared between different IVDH grades and their prognostic value was investigated. RESULTS: pNF-H levels were significantly greater in Grade 5 than Grade 4 dogs. There were significant differences in pNF-H levels between dogs that regained voluntarily ambulation and those that did not. All 8 dogs that had high pNF-H levels 1-3 days after injury did not regain the ability to walk after surgery. CONCLUSIONS: Serum pNF-H levels might be a biomarker for predicting prognosis of canine SCI.

Clinical features of early recurrence of type I thoracolumbar intervertebral disk herniation in Miniature Dachshunds.

Some reports have been published on clinical features in dogs with early recurrence of type I thoracolumbar intervertebral disk herniation (TL-IVDH), but there is little understanding of the changes involved. This retrospective study describes the clinical features, including radiographic image results at the time of recurrence, of dogs with type I TL-IVDH that had undergone hemilaminectomy but then suffered early recurrence. Our medical records were searched between June 2007 and December 2022. Nine dogs showed deterioration in neurological signs within 4 to 6 weeks after surgery. All nine were Miniature Dachshunds. Radiographic images at initial onset showed calcification at the affected intervertebral disk space in all 9 dogs. Disk herniations at the initial onset were located between T11-12 and L1-2. After the first surgery, neurological function improved in all dogs. Recurrence occurred at the same site as at initial onset in all dogs. No calcification was observed at the affected intervertebral disk space on images at the time of recurrence. The extruded disk materials were surgically removed, and neurological function improved after the second surgery. In conclusion, calcification at the affected disk space at the time of initial onset is indicative of residual nucleus materials not yet fully extruded, and is a risk factor for early recurrence of type I TL-IVDH.

A feline spinal dermoid cyst treated with surgical intervention.

A 5-year-old neutered female mixed cat presented with reduced activity and ataxia of the hind limbs. Computed tomography and magnetic resonance imaging revealed an extradural mass compressing the spinal cord on the dorsal aspects from the 7th to 8th thoracic vertebra. Dorsal laminectomy was performed on the 7-8th thoracic vertebra and the cyst was totally removed, giving full resolution of the clinical signs. The cyst was diagnosed as a dermoid cyst. To our knowledge, this is the first report of feline dermoid cyst compressing the spinal cord that was diagnosed antemortem. The prognosis is favorable when the cyst is completely resected.

Administration of TSG-6 improves memory after traumatic brain injury in mice.

Traumatic brain injury (TBI) causes multiple long-term defects including a loss of working memory that is frequently incapacitating. Administrations of mesenchymal stem/stromal cells (MSCs) previously produced beneficial effects in models of TBI as well as other disease models. In several models, the beneficial effects were explained by the MSCs being activated to express TSG-6, a multifunctional protein that modulates inflammation. In a mouse model of TBI, we found the initial mild phase of the inflammatory response persisted for at least 24h and was followed by secondary severe response that peaked at 3days. Intravenous human MSCs or TSG-6 during initial mild phase decreased neutrophil extravasation, expression of matrix metalloproteinase 9 by endothelial cells and neutrophils, and the subsequent blood brain barrier leakage in secondary phase. Administration of TSG-6 also decreased the lesion size at 2weeks. Importantly, the acute administration of TSG-6 within 24h of TBI was followed 6 to 10weeks later by improvements in memory, depressive-like behavior and the number of newly born-neurons. The data suggested that acute administration of TSG-6 may be an effective therapy for decreasing some of the long-term consequences of TBI.