Hitos/Milestones

🇪🇦El uso combinado y secuencial de células madre mesenquimales y neurales permite restaurar el epéndimo dañado tras hemorragias ventriculares.

🇬🇧The combined and sequential use of mesenchymal and neural stem cells allows for the restoration of the damaged ependyma following ventricular hemorrhages.

Design of a stem cell-based therapy for ependymal repair in hydrocephalus associated with germinal matrix hemorrhages. Rodriguez-Perez LM, Ojeda-Pérez B, López-de-San-Sebastián J, García-Bonilla M, González-García M, Fernández-Muñoz B, Sánchez-Pernaute R, García-Martín ML, Domínguez-Pinos D, Cárdenas-García C, Jiménez AJ, Paez-Gonzalez P. Stroke. 2024; 55(4):1062-1074.

🇪🇦El tratamiento con células madre mesenquimales induce neuroprotección en la corteza cerebral afectada por hidrocefalia congénita.

🇬🇧Treatment with mesenchymal stem cells induces neuroprotection in the cerebral cortex affected by congenital hydrocephalus. 

Generation of Periventricular Reactive Astrocytes Overexpressing Aquaporin 4 Is Stimulated by Mesenchymal Stem Cell Therapy. García-Bonilla M, Ojeda-Pérez B, Shumilov K, Rodríguez-Pérez LM, Domínguez-Pinos D, Vitorica J, Jiménez S, Ramírez-Lorca R, Echevarría M, Cárdenas-García C, Iglesias T, Gutiérrez A, McAllister JP 2nd, Limbrick DD Jr, Páez-González P, Jiménez AJ. International Journal of Molecular Sciences. 2023 Mar 15;24(6):5640.

Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells.  García-Bonilla M; Ojeda B; García Martin MA; Muñoz Hernández M; Vitorica J; Sebastián Jiménez; Leonor Santos-Ruiz; Kirill Shumilov; Silvia Claros; Antonia Gutiérrez; Páez-González & Jiménez Lara AJ. Stem Cell Research and Therapy 2019; 11, 121.

🇪🇦Existen biomarcadores que nos pueden dar un pronóstico sobre la gravedad con la que cursará la hidrocefalia y nos pueden permitir seleccionar el tratamiento más adecuado de forma temprana.

🇬🇧There are biomarkers that can provide a prognosis on the severity of hydrocephalus progression and allow us to select the most appropriate treatment early on.

Identification of key molecular biomarkers involved in reactive and neurodegenerative processes present in inherited congenital hydrocephalus. Betsaida Ojeda-Pérez B, Campos-Sandoval JA, García-Bonilla M, Cárdenas-García C, Páez- González P & Jiménez-Lara AJ. Fluids Barriers CNS 2021; 18, 30

 A distinct metabolite profile correlates with neurodegenerative conditions and the severity of congenital hydrocephalus. García-Bonilla M; María Luisa García-Martin ML; Muñoz Hernández MC; Domínguez Pinos MD; Peñalver; Castilla L; Alonso FJ; Márquez J; Shumilov K; Hidalgo-Sánchez R; Gutiérrez A; Páez-González P & Jiménez Lara, AJ. Journal of Neuropathology Experimental Neurology, 2018; 77(12), 1122–1136

Increased levels of tumour necrosis factor alpha (TNFα) but not transforming growth factor-beta 1 (TGFβ1) are associated with the severity of congenital hydrocephalus in the hyh mouse. Jiménez AJ, Rodríguez-Pérez LM, Domínguez-Pinos MD, Gómez-Roldán MC, García-Bonilla M, Ho-Plagaro A, Roales-Buján R, Jiménez S, Roquero-Mañueco MC, Martínez-León MI, García-Martín ML, Cifuentes M, Ros B, Arráez MÁ, Vitorica J, Gutiérrez A, Pérez-Fígares JM. Neuropathol Appl Neurobiol. 2014; 40(7): 911-32.

🇪🇦La alteración del desarrollo normal del epéndimo es un factor determinante tanto en el origen como en la evolución de la hidrocefalia. La protección del epéndimo y su regeneración son aspectos terapéuticamente clave en el tratamiento de esta patología.

🇬🇧The alteration of normal ependymal development is a determining factor in both the origin and the evolution of hydrocephalus. The protection of the ependyma and its regeneration are key therapeutic aspects in the treatment of this pathology.

Uncovering inherent cellular plasticity of multiciliated ependyma leading to ventricular wall transformation and hydrocephalus. Abdi K, Paez-Gonzalez P, Lay M, Pyun J, Kuo CT. Uncovering inherent cellular plasticity of multiciliated ependyma leading to ventricular wall transformation and hydrocephalus. Nat Commun. 2018 Apr 25;9(1):1655.

Ventricular Zone Disruption in Human Neonates With Intraventricular Hemorrhage. McAllister JP, Guerra MM, Ruiz LC, Jimenez AJ, Dominguez-Pinos D, Sival D, den Dunnen W, Morales DM, Schmidt RE, Rodriguez EM, Limbrick DD. J Neuropathol Exp Neurol. 2017, 1; 76(5): 358-375.

Ependymal denudation and alterations of the subventricular zone occur in human fetuses with a moderate communicating hydrocephalus. Domínguez-Pinos MD, Páez P, Jiménez AJ, Weil B, Arráez MA, Pérez-Fígares JM, Rodríguez EM. J Neuropathol Exp Neurol. 2005; 64(7): 595-604.

Cellular mechanisms involved in the stenosis and obliteration of the cerebral aqueduct of hyh mutant mice developing congenital hydrocephalus. Wagner C, Batiz LF, Rodríguez S, Jiménez AJ, Páez P, Tomé M, Pérez-Fígares JM, Rodríguez EM. J Neuropathol Exp Neurol. 2003; 62(10): 1019-40.

A programmed ependymal denudation precedes congenital hydrocephalus in the hyh mutant mouse. Jiménez AJ, Tomé M, Páez P, Wagner C, Rodríguez S, Fernández-Llebrez P, Rodríguez EM, Pérez-Fígares JM. J Neuropathol Exp Neurol. 2001; 60(11): 1105-19.

Spontaneous congenital hydrocephalus in the mutant mouse hyh. Changes in the ventricular system and the subcommissural organ. Pérez-Fígares JM, Jiménez AJ, Pérez-Martín M, Fernández-Llebrez P, Cifuentes M, Riera P, Rodríguez S, Rodríguez EM. J Neuropathol Exp Neurol. 1998; 57(2): 188-202.

Ependymal denudation, aqueductal obliteration and hydrocephalus after a single injection of neuraminidase into the lateral ventricle of adult rats. Grondona JM, Pérez-Martín M, Cifuentes M, Pérez J, Jiménez AJ, Pérez-Fígares JM, Fernández-Llebrez P. J Neuropathol Exp Neurol. 1996; 55(9): 999-1008.

🇪🇦Como consecuencia de la alteración en el desarrollo del epéndimo concurrente con la hidrocefalia, se afecta la neurogénesis. Esto puede explicar daños cognitivos permanentes posteriores en niños que padecen esta patología.

🇬🇧As a consequence of the alteration in ependymal development concurrent with hydrocephalus, neurogenesis is affected. This may explain subsequent permanent cognitive damage in children suffering from this pathology.

Cholinergic Circuit Control of Postnatal Neurogenesis Asrican B, Paez-Gonzalez P, Erb J, Kuo CT. (Austin). Neurogenesis 2016;3(1)

Identification of distinct CHAT (+) neurons and activity dependent control of postnatal SVZ neurogenesis. Páez-González P; Asrican B; Rodríguez E; Kuo CT. Nat Neurosci. (2014) Jul;17(7):934-42.

Disruption of the neurogenic niche in the subventricular zone of postnatal hydrocephalic hyh mice. Jiménez AJ, García-Verdugo JM, González CA, Bátiz LF, Rodríguez-Pérez LM, Páez P, Soriano-Navarro M, Roales-Buján R, Rivera P, Rodríguez S, Rodríguez EM, Pérez-Fígares JM. J Neuropathol Exp Neurol. 2009; 68(9): 1006-20.

🇪🇦Como consecuencia de la alteración que sufre el epéndimo durante la hidrocefalia, los astrocitos periventriculares presentan cambios citológicos y metabólicos que conducen a la producción de nuevas moléculas con efecto protector. Esto hace cuestionar en enfoque terapéutico en el que se determina que la astrogliosis es siempre negativa.

🇬🇧As a consequence of the alteration the ependyma undergoes during hydrocephalus, periventricular astrocytes present cytological and metabolic changes that lead to the production of new molecules with a protective effect. This questions the therapeutic approach that determines astrogliosis is always negative.

Increased levels of tumour necrosis factor alpha (TNFα) but not transforming growth factor-beta 1 (TGFβ1) are associated with the severity of congenital hydrocephalus in the hyh mouse. Jiménez AJ, Rodríguez-Pérez LM, Domínguez-Pinos MD, Gómez-Roldán MC, García-Bonilla M, Ho-Plagaro A, Roales-Buján R, Jiménez S, Roquero-Mañueco MC, Martínez-León MI, García-Martín ML, Cifuentes M, Ros B, Arráez MÁ, Vitorica J, Gutiérrez A, Pérez-Fígares JM. Neuropathol Appl Neurobiol. 2014; 40(7): 911-32.

Astrocytes acquire morphological and functional characteristics of ependymal cells following disruption of ependyma in hydrocephalus. Roales-Buján R, Páez P, Guerra M, Rodríguez S, Vío K, Ho-Plagaro A, García-Bonilla M, Rodríguez-Pérez LM, Domínguez-Pinos MD, Rodríguez EM, Pérez-Fígares JM, Jiménez AJ. Acta Neuropathol. 2012; 124(4): 531-46.

🇪🇦Defectos en las uniones celulares en el epéndimo en desarrollo parecen ser claves para la aparición de la hidrocefalia, tanto en humanos como en distintos modelos animales.

🇬🇧Defects in cellular junctions in the developing ependyma appear to be key to the onset of hydrocephalus, both in humans and in various animal models.

Cell Junction Pathology of Neural Stem Cells Is Associated With Ventricular Zone Disruption, Hydrocephalus, and Abnormal Neurogenesis. Guerra MM, Henzi R, Ortloff A, Lichtin N, Vío K, Jiménez AJ, Dominguez-Pinos MD, González C, Jara MC, Hinostroza F, Rodríguez S, Jara M, Ortega E, Guerra F, Sival DA, den Dunnen WF, Pérez-Fígares JM, McAllister JP, Johanson CE, Rodríguez EM. J Neuropathol Exp Neurol. 2015; 74(7): 653-71.

Structure and function of the ependymal barrier and diseases associated with ependyma disruption. Jiménez AJ, Domínguez-Pinos MD, Guerra MM, Fernández-Llebrez P, Pérez-Fígares JM. Tissue Barriers. 2014; 19; 2:e28426.

A cell junction pathology of neural stem cells leads to abnormal neurogenesis and hydrocephalus. Rodríguez EM, Guerra MM, Vío K, González C, Ortloff A, Bátiz LF, Rodríguez S, Jara MC, Muñoz RI, Ortega E, Jaque J, Guerra F, Sival DA, den Dunnen WF, Jiménez AJ, Domínguez-Pinos MD, Pérez-Fígares JM, McAllister JP, Johanson C. Biol Res. 2012; 45(3): 231-42.

🇪🇦El desarrollo del epéndimo en la hidrocefalia congénita condiciona el grado afectación de las cavidades ventriculares.

🇬🇧Ependymal development in congenital hydrocephalus determines the degree of involvement of the ventricles.

New ependymal cells are born postnatally in two discrete regions of the mouse brain and support ventricular enlargement in hydrocephalus. Bátiz LF, Jiménez AJ, Guerra M, Rodríguez-Pérez LM, Toledo CD, Vio K, Páez P, Pérez-Fígares JM, Rodríguez EM. Acta Neuropathol. 2011; 121(6): 721-35.

🇪🇦Asociados a la hidrocefalia congénita, existen fenómenos neurodegenerativos comunes y que deben ser de intervención terapéutica si se intentan desarrollar estrategias terapéuticas.

🇬🇧Associated with congenital hydrocephalus, there are common neurodegenerative phenomena that must be the target of therapeutic intervention when attempting to develop therapeutic strategies.

A simple PCR-based genotyping method for M105I mutation of alpha-SNAP enhances the study of early pathological changes in hyh phenotype.Bátiz LF, Roales-Buján R, Rodríguez-Pérez LM, Matas IM, Páez P, Roque M, Jiménez AJ, Ramos C, Pérez-Fígares JM. ol Cell Probes. 2009; 23(6): 281-90

Patterned neuropathologic events occurring in hyh congenital hydrocephalic mutant mice. Páez P, Bátiz LF, Roales-Buján R, Rodríguez-Pérez LM, Rodríguez S, Jiménez AJ, Rodríguez EM, Pérez-Fígares JM. J Neuropathol Exp Neurol. 2007; 66(12): 1082-92.

Heterogeneous expression of hydrocephalic phenotype in the hyh mice carrying a point mutation in alpha-SNAP. Bátiz LF, Páez P, Jiménez AJ, Rodríguez S, Wagner C, Pérez-Fígares JM, Rodríguez EM. Neurobiol Dis.2006; 23(1): 152-68.