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Hippocampal seizures mimicking mesial temporal lobe epilepsy cause a profound disruption of the adult neurogenic niche in mice. Seizures provoke neural stem cells to switch to a reactive phenotype (reactive neural stem cells, React-NSCs) characterized by multibranched hypertrophic morphology, massive activation to enter mitosis, symmetric division, and final differentiation into reactive astrocytes. As a result, neurogenesis is chronically impaired. Here, using a mouse model of mesial temporal lobe epilepsy, we show that the epidermal growth factor receptor (EGFR) signaling pathway is key for the induction of React-NSCs and that its inhibition exerts a beneficial effect on the neurogenic niche. We show that during the initial days after the induction of seizures by a single intrahippocampal injection of kainic acid, a strong release of zinc and heparin-binding epidermal growth factor, both activators of the EGFR signaling pathway in neural stem cells, is produced. Administration of the EGFR inhibitor gefitinib, a chemotherapeutic in clinical phase IV, prevents the induction of React-NSCs and preserves neurogenesis., (© 2024 Pastor-Alonso et al.)

Background: Both vedolizumab and ustekinumab are approved for the management of Crohn's disease [CD]. Data on which one would be the most beneficial option when anti-tumour necrosis factor [anti-TNF] agents fail are limited., Aims: To compare the durability, effectiveness, and safety of vedolizumab and ustekinumab after anti-TNF failure or intolerance in CD., Methods: CD patients from the ENEIDA registry who received vedolizumab or ustekinumab after anti-TNF failure or intolerance were included. Durability and effectiveness were evaluated in both the short and the long term. Effectiveness was defined according to the Harvey-Bradshaw index [HBI]. The safety profile was compared between the two treatments. The propensity score was calculated by the inverse probability weighting method to balance confounder factors., Results: A total of 835 patients from 30 centres were included, 207 treated with vedolizumab and 628 with ustekinumab. Dose intensification was performed in 295 patients. Vedolizumab [vs ustekinumab] was associated with a higher risk of treatment discontinuation (hazard ratio [HR] 2.55, 95% confidence interval [CI]: 2.02-3.21), adjusted by corticosteroids at baseline [HR 1.27; 95% CI: 1.00-1.62], moderate-severe activity in HBI [HR 1.79; 95% CI: 1.20-2.48], and high levels of C-reactive protein at baseline [HR 1.06; 95% CI: 1.02-1.10]. The inverse probability weighting method confirmed these results. Clinical response, remission, and corticosteroid-free clinical remission were higher with ustekinumab than with vedolizumab. Both drugs had a low risk of adverse events with no differences between them., Conclusion: In CD patients who have failed anti-TNF agents, ustekinumab seems to be superior to vedolizumab in terms of durability and effectiveness in clinical practice. The safety profile is good and similar for both treatments., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Infliximab seems to be the most efficacious of the three available anti-TNF agents for ulcerative colitis (UC) but little is known when it is used as the second anti-TNF., Objectives: To compare the clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in UC patients., Design: Retrospective observational study., Methods: Patients from the ENEIDA registry treated consecutively with infliximab and a subcutaneous anti-TNF (or vice versa), naïve to other biological agents, were identified and grouped according to the administration route of the first anti-TNF into IVi (intravenous initially) or SCi (subcutaneous initially)., Results: Overall, 473 UC patients were included (330 IVi and 143 SCi). Clinical response at week 14 was 42.7% and 48.3% in the IVi and SCi groups (non-statistically significant), respectively. Clinical remission rates at week 52 were 32.8% and 31.4% in the IVi and SCi groups (nonsignificant differences), respectively. A propensity-matched score analysis showed a higher clinical response rate at week 14 in the SCi group and higher treatment persistence in the IVi group. Regarding long-term outcomes, dose escalation and discontinuation due to the primary failure of the first anti-TNF and more severe disease activity at the beginning of the second anti-TNF were inversely associated with clinical remission., Conclusion: The use of a second anti-TNF for UC seems to be reasonable in terms of efficacy, although it is particularly reduced in the case of the primary failure of the first anti-TNF. Whether the second anti-TNF is infliximab or subcutaneous does not seem to affect efficacy., Competing Interests: MC has served as a speaker for Takeda, Janssen, Faes Farma, and MSD; FC has served as a speaker or has received educational grants from Takeda, Janssen, MSD, and Ferring; MR has served as a speaker or has received research or educational funding or advisory fees from MSD, Abbvie, Pfizer, Takeda, and Janssen; MI has served as a speaker or has received research or educational funding or advisory fees from MSD, Janssen, Adacyte, and Takeda; LC has served as a speaker or has received research or educational funding or advisory fees from Abbvie, Dr. Falk Pharma, and Tillots Pharma; LB has served as a speaker or has received research or educational funding or advisory fees from Ikan Biotech; MBA has served as a speaker or has received research or educational funding or advisory fees from MSD, AbbVie, Janssen, Kern Pharma, Celltrion, Takeda, Gillead, Celgene, Pfizer, Sandoz, Biogen, Fresenius, Ferring, Faes Farma, Dr. Falk Pharma, Chiesi, Gebro Pharma, Adacyte, and Vifor Pharma; CG-M has received educational funding fees from AbbVie, Janssen, Pfizer, Ferring, Kern Pharma, Norgine, and Tillots Pharma; JMH has served as a speaker or has received research or educational funding or advisory fees from Merck Sharp & Dohme, Ferring, Abbvie, Janssen, Biogen, Sandoz, Kern Pharma, Faes Farma, Vifor Pharma, and Takeda; RL has served as a speaker or has received research or educational funding or advisory fees from MSD, Abbvie, Pfizer, Takeda, Janssen, and Dr. Falk; AM-C has received research or educational funding from Abbvie, Biogen, Ferring, Janssen, MSD, Takeda, Dr. Falk Pharma, and Tillotts; JPG has served as a speaker or has received research or educational funding or advisory fees from MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos, Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine, and Vifor Pharma; FG has served as a speaker or has received research or educational funding or advisory fees from Faes-Farma, Galápagos, Takeda, Pfizer, Janssen, and Abbvie; PA has served as a speaker or has received research or educational funding or advisory fees from MSD, Abbvie, Takeda, Janssen, Gebro Pharma, Tillotts Pharma, and Biogen; CT has served as a speaker or has received research or educational funding or advisory fees from MSD, AbbVie, Pfizer, Takeda, Janssen, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Galapagos, and Tillots; IR-L has served as a speaker or has received research or educational funding or advisory fees from MSD, Pfizer, Abbvie, Takeda, Janssen, Tillotts Pharma, Kern, Celltrion, Roche, Ferring, Dr. Falk Pharma, Galapagos, Otsuka Pharmaceutical, and Adacyte; MM has served as a speaker and has received research or educational funding from MSD, AbbVie, Takeda, Janssen, Ferring, and Pfizer; ED has served as a speaker or has received research or educational funding or advisory fees from AbbVie, Adacyte Therapeutics, Biogen, Celltrion, Galapagos, Gilead, Janssen, Kern Pharma, MSD, Pfizer, Roche, Samsung, Takeda, and Tillots; MJG has served as a speaker or has received research or educational funding or advisory fees from Janssen, Pfizer, Abbvie, Takeda, Kern Pharma, and Ferring; MA has served as a speaker or has received research or educational funding or advisory fees from Faes, Ferring, and Janssen, and received educational grants from Janssen; JRP has served as a speaker or has received research or educational funding or advisory fees from MSD, AbbVie, and Tillots Pharma; FB received educational funding fees from AbbVie, Janssen, Pfizer, Ferring, Kern Pharma, Norgine, and Tillots Pharma. The remaining authors declared no conflicts of interest., (© The Author(s), 2024.)

The prevalence of central nervous system (CNS) dysfunction as a result of disease or trauma remains a clinically unsolved problem which is raising increased awareness in our aging society. Human Dental Pulp Stem Cells (hDPSCs) are excellent candidates to be used in tissue engineering and regenerative therapies of the CNS due to their neural differentiation ability and lack of tumorigenicity. Accordingly, they have been successfully used in animal models of spinal cord injury, stroke and peripheral neuropathies. The ideal therapy in brain injury should combine strategies aiming to protect the damaged lesion and, at the same time, accelerate brain tissue regeneration, thus promoting fast recovery while minimizing side or long-term effects. The use of bioresorbable nanopatterned poly(lactide-co-ɛ-caprolactone) (PLCL) polymeric scaffolds as hDPCSs carriers can represent an advantage for tissue regeneration. In this chapter, we describe the surgical procedures to implant functionalized bioresorbable scaffolds loaded with hDPSCs to improve the brain lesion microenvironment in an intracranial stab wound injury model severing the rostral migratory stream (RMS) that connects the brain subventricular zone (SVZ) and the olfactory bulb in nude mice. Additionally, we also describe the technical steps after animal sacrifice for histological tissue observation and characterization., Competing Interests: Disclosures I.M.R., Y.P., B.P.R., J.L., R.B.T., D.M.A., I.R., S.M.C., J.M., L.G.S., G.I., F.L., Y.H., C.E., A.L., J.R.P. have no conflict of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)