Navegando por Palavras-chave "Traumatic brain injury"
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- ItemAcesso aberto (Open Access)Chondroitin Sulfate Impairs Neural Stem Cell Migration Through ROCK Activation(Humana Press Inc, 2018) Galindo, Layla Testa [UNIFESP]; Mundim, Mayara T. V. V. [UNIFESP]; Pinto, Agnes S. [UNIFESP]; Chiarantin, Gabrielly Maria Denadai [UNIFESP]; Almeida, Maira E. S.; Lamers, Marcelo L.; Horwitz, Alan R.; Santos, Marinilce F.; Porcionatto, Marimélia Aparecida [UNIFESP]Brain injuries such as trauma and stroke lead to glial scar formation by reactive astrocytes which produce and secret axonal outgrowth inhibitors. Chondroitin sulfate proteoglycans (CSPG) constitute a well-known class of extracellular matrix molecules produced at the glial scar and cause growth cone collapse. The CSPG glycosaminoglycan side chains composed of chondroitin sulfate (CS) are responsible for its inhibitory activity on neurite outgrowth and are dependent on RhoA activation. Here, we hypothesize that CSPG also impairs neural stem cell migration inhibiting their penetration into an injury site. We show that DCX+ neuroblasts do not penetrate a CSPG-rich injured area probably due to Nogo receptor activation and RhoA/ROCK signaling pathway as we demonstrate in vitro with neural stem cells cultured as neurospheres and pull-down for RhoA. Furthermore, CS-impaired cell migration in vitro induced the formation of large mature adhesions and altered cell protrusion dynamics. ROCK inhibition restored migration in vitro as well as decreased adhesion size.
- ItemSomente MetadadadosFluid Resuscitation With Isotonic or Hypertonic Saline Solution Avoids Intraneural Calcium Influx After Traumatic Brain Injury Associated With Hemorrhagic Shock(Lippincott Williams & Wilkins, 2010-04-01) Balbino, Marcos; Capone Neto, Antonio; Prist, Ricardo; Ferreira, Alice Teixeira [UNIFESP]; Poli-de-Figueiredo, Luiz F.; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)Background: Calcium is one of the triggers involved in ischemic neuronal death. Because hypotension is a strong predictor of outcome in traumatic brain injury (TBI), we tested the hypothesis that early fluid resuscitation blunts calcium influx in hemorrhagic shock associated to TBI.Methods: Fifteen ketamine-halothane anesthetized mongrel dogs (18.7 kg +/- 1.4 kg) underwent unilateral cryogenic brain injury. Blood was shed in 5 minutes to a target mean arterial pressure of 40 mm Hg to 45 mm Hg and maintained at these levels for 20 minutes (shed blood volume = 26 mL/kg +/- 7 mL/kg). Animals were then randomized into three groups: CT (controls, no fluid resuscitation), HS (7.5% NaCl, 4 mL/kg, in 5 minutes), and LR (lactate Ringer's, 33 mL/kg, in 15 minutes). Twenty minutes later, a craniotomy was performed and cerebral biopsies were obtained next to the lesion (clinical penumbra) and from the corresponding contralateral side (lesion's mirror) to determine intracellular calcium by fluorescence signals of Fura-2-loaded cells.Results: Controls remained hypotensive and in a low-flow state, whereas fluid resuscitation improved hemodynamic profile. There was a significant increase in intracellular calcium in the injured hemisphere in CT (1035 nM +/- 782 nM), compared with both HS (457 nM +/- 149 nM, p = 0.028) and LR (392 nM +/- 178 nM, p = 0.017), with no differences between HS and LR (p = 0.38). Intracellular calcium at the contralateral, uninjured hemisphere was 438 nM +/- 192 nM in CT, 510 nM +/- 196 nM in HS, and 311 nM +/- 51 nM in LR, with no significant differences between them.Conclusion: Both small volume hypertonic saline and large volume lactated Ringer's blunts calcium influx in early stages of TBI associated to hemorrhagic shock. No fluid resuscitation strategy promotes calcium influx and further neural damage.
- ItemEmbargomiR‑9‑5p is downregulated in serum extracellular vesicles of patients treated with biperiden after traumatic brain injury(Universidade Federal de São Paulo, 2024-08-23) Kajitani, Gustavo Satoru [UNIFESP]; Belangero, Sintia Iole Nogueira [UNIFESP]; http://lattes.cnpq.br/2623781262478620; http://lattes.cnpq.br/3744655540260834Traumatic brain injury (TBI) is a prevalent and debilitating condition, which often leads to the development of posttraumatic epilepsy (PTE), a condition that yet lacks preventive strategies. Biperiden, an anticholinergic drug, is a promising candidate that has shown efficacy in murine models of PTE. MicroRNAs (miRNAs), small regulatory RNAs, can help in understanding the biological basis of PTE and act as TBIand PTErelevant biomarkers that can be detected peripherally, as they are present in extracellular vesicles (EVs) that cross the bloodbrain barrier. This study aimed to investigate miRNAs in serum EVs from patients with TBI, and their association with biperiden treatment and PTE. Blood samples of 37 TBI patients were collected 10 days after trauma and treatment initiation in a doubleblind clinical trial. A total of 18 patients received biperiden, with three subjects developing PTE, and 19 received placebo, with two developing PTE. Serum EVs were characterized by size distribution and protein profiling, followed by highthroughput sequencing of the EV miRNome. Differential expression analysis revealed no significant differences in miRNA expression between TBI patients with and without PTE. Interestingly, miR95p displayed decreased expression in biperidentreated patients compared to the placebo group. This miRNA regulates genes enriched in stress response pathways, including axonogenesis and neuronal death, relevant to both PTE and TBI. These findings indicate that biperiden may alter miR95p expression in serum EVs, which may play a role in TBI resolution.
- ItemAcesso aberto (Open Access)Notch, Wnt and Shh neurogenic signaling co-regulation in reactive astrocyte response(Universidade Federal de São Paulo, 2022-05-09) Delgado-Garcia, Lina Maria [UNIFESP]; Porcionatto, Marimelia Aparecida [UNIFESP]; López-Mascaraque, Laura; http://lattes.cnpq.br/6155537170968904; http://lattes.cnpq.br/9266631373645740After a TBI, the neural network activates a reparative response seeking to restore homeostasis in the affected area. Astrocyte reactivation is an essential component of this response. Understanding astroglial cell functional heterogeneity and dissecting the role of supportive molecules in brain damage is crucial for our current comprehension of the mechanisms leading to the repair and regeneration of the CNS and the development of novel therapeutic interventions. In this thesis, we study cellular and molecular aspects of reactive astrocytes and Notch, Wnt and Shh neurogenic signaling modulation response. We used an in vivo model of brain damage by TBI and an in vitro model of wound healing and astrocyte reactivation by scratch. We found Notch (NICD) and Wnt (active β-catenin) upregulation and described signaling concentration patterns in the cortex of mice submitted to TBI. Reactive astrocytes presented an aggregated distribution in the core of Notch signaling. We evaluated the functional heterogeneity and plasticity of the progeny of E14 mice -GFAP StarTrack in utero electroporated active neural progenitors. Lower layer protoplasmic astrocytes showed a strong reactive response. Upper and lower layers protoplasmic reactive astrocytes close to the lesion borders showed increased polarization and enrichment of mesh-like structures. In vitro treatment with LY450139 Semagacestat inhibited Notch - HEY signaling. Notch inhibition may attenuate reactive astrocytes response and activate neural precursor mechanisms. Finally, we suggest indirect co-regulation of Wnt-Shh signaling in BHLH-Notch target genes after Notch inhibition. Similarly, Notch inhibition may also have a supportive effect in Wnt-Shh signaling activation. Above all, this thesis contributes to increasing our knowledge of glia biology and the regenerative role of neurogenic signaling molecules in the response of reactive astrocytes after brain injury.
- ItemSomente MetadadadosValue of Repeat Cranial Computed Tomography in Pediatric Patients Sustaining Moderate to Severe Traumatic Brain Injury(Lippincott Williams & Wilkins, 2008-12-01) Lucas da Silva, Paulo Sergio; Reis, Maria Eunice; Aguiar, Vania Euzebio; Universidade Federal de São Paulo (UNIFESP)Background: Repeat head computed tomography (CT) is standard practice for traumatic brain injury (TBI) at many centers. the few studies available in children remain unclear over the value of repeat CT within 24 hours to 48 hours of lesion in such patients. the purpose of the present study was to assess the value of repeat cranial CT in children presenting moderate or severe TBI.Methods: A retrospective study performed within a pediatric intensive care unit between January 2000 and December 2006. All patients with moderate and severe TBI who survived the first 24 hours after admission were included. Clinical data collected included age, lesion mechanism, time between first and second CTs, disease severity score at admission, and Glasgow Coma Scale (GCS) both at admission and (lay of repeat CT.Results: A total of 63 children were assessed whose mean age was 72 months (48-112). the time between the first and the second CT scans averaged 25.78 hours +/- 13.75 hours (range, 6-48 hours). the reasons for ordering repeat CT scans were divided as follows: follow-up (78%), neurologic deterioration (20.4%.), and increased intracranial pressure (1.6%). the change on the follow-tip CT scan was compared with the GCS score. the GCS score was improved in 66.6% of patients, remained the same in 15.9%, and worsened in 17.5%. the appearance on the CT scans was better, the same or worse in 41.3%, 34.9%, and 23.8% of patients, respectively. There was a significant association between GCS and changes in findings on repeat CT (OR = 34.5, confidence interval [5.98-199.04], p = 0.000009). the positive and negative predictive values were 82% and 89%, respectively. One patient with a worsened GCS required surgical intervention based on the repeat CT scan.Conclusion: An unchanged or improving neurologic examination in children sustaining moderate or severe TBI who are appropriately monitored may be adequate to exclude the possibility of neurosurgical intervention and, hence, repeat head CT scan.