THE ROLE OF THE SVZ IN ISCHEMIC CONDITION. / Rossetti, Tiziana.

2012. 213 p.

Research output: ThesisDoctoral Thesis

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THE ROLE OF THE SVZ IN ISCHEMIC CONDITION. / Rossetti, Tiziana.

2012. 213 p.

Research output: ThesisDoctoral Thesis

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@phdthesis{06b163d45c934f31981015252ddd16d7,
title = "THE ROLE OF THE SVZ IN ISCHEMIC CONDITION",
abstract = "The occlusion of a cerebral artery or stroke often results in neuronal deficitand/or patient death. A partial recovery often follows non-fatal stroke andthis may be due to the activation of the progenitor cells in the Sub-Ventricular Zone (SVZ) naturally occurring after ischemia. In order toclarify the role of the SVZ neurogenesis in animal recovery, the effect ofneurogenesis inhibition and boosting were studied in the mouse MiddleCerebral Artery occlusion model (MCAo). 6 to 10-week-old male micewere pre-treated with intracranial injections of lentiviral vector (LV) orintegration deficient lentiviral vectors (IDLV), in order to target the SVZ.The IDLV carried an expression cassette encoding for a precursor Glialcell-derived neurotrophic factor (GDNF) or the tetanus toxin fragment C(TTC), which recently has been demonstrated to have growth factor likebehaviour. Another group of animals received the LV carrying a doublepromoter expression cassette encoding for an eGFP, and in order to inhibitthe cell cycle in targeted cells the shRNA_Cyclin D1. All vectors wereco-injected with the LV_ pHR{\textquoteright}SIN-cPPT-SEW, which contains an eGFPcassette. Two weeks later the animals received the MCAo, and for threeweeks the sensorimotor behaviour was tested. Neurological assessmentshowed the sensory-motor debilitation was significant increased after thetreatment with the LV_shRNA_CyclinD1 (* p<0.05); the IDLV_GDNFand IDLV_TTC groups showed a trend to improve neurological deficit inthe subjects alive until day 5. In the IDLV_GDNF, the SVZ{\textquoteright}s derivedgreen cells were positively correlated with the ischemic volume, *p<0.05R=0.68, and the neurodegeneration, ***p<0.001 R=0.92. Moreover, whilethe SVZ neurogenesis inhibition reduced life expectancy, the boostingsignificantly improved it. Immunofluorescence analysis showed amigration extended to the striatum and cortex with a max distance of 1.87mm from the SVZ.",
author = "Tiziana Rossetti",
year = "2012",
language = "English",

}

RIS

TY - THES

T1 - THE ROLE OF THE SVZ IN ISCHEMIC CONDITION

AU - Rossetti, Tiziana

PY - 2012

Y1 - 2012

N2 - The occlusion of a cerebral artery or stroke often results in neuronal deficitand/or patient death. A partial recovery often follows non-fatal stroke andthis may be due to the activation of the progenitor cells in the Sub-Ventricular Zone (SVZ) naturally occurring after ischemia. In order toclarify the role of the SVZ neurogenesis in animal recovery, the effect ofneurogenesis inhibition and boosting were studied in the mouse MiddleCerebral Artery occlusion model (MCAo). 6 to 10-week-old male micewere pre-treated with intracranial injections of lentiviral vector (LV) orintegration deficient lentiviral vectors (IDLV), in order to target the SVZ.The IDLV carried an expression cassette encoding for a precursor Glialcell-derived neurotrophic factor (GDNF) or the tetanus toxin fragment C(TTC), which recently has been demonstrated to have growth factor likebehaviour. Another group of animals received the LV carrying a doublepromoter expression cassette encoding for an eGFP, and in order to inhibitthe cell cycle in targeted cells the shRNA_Cyclin D1. All vectors wereco-injected with the LV_ pHR’SIN-cPPT-SEW, which contains an eGFPcassette. Two weeks later the animals received the MCAo, and for threeweeks the sensorimotor behaviour was tested. Neurological assessmentshowed the sensory-motor debilitation was significant increased after thetreatment with the LV_shRNA_CyclinD1 (* p<0.05); the IDLV_GDNFand IDLV_TTC groups showed a trend to improve neurological deficit inthe subjects alive until day 5. In the IDLV_GDNF, the SVZ’s derivedgreen cells were positively correlated with the ischemic volume, *p<0.05R=0.68, and the neurodegeneration, ***p<0.001 R=0.92. Moreover, whilethe SVZ neurogenesis inhibition reduced life expectancy, the boostingsignificantly improved it. Immunofluorescence analysis showed amigration extended to the striatum and cortex with a max distance of 1.87mm from the SVZ.

AB - The occlusion of a cerebral artery or stroke often results in neuronal deficitand/or patient death. A partial recovery often follows non-fatal stroke andthis may be due to the activation of the progenitor cells in the Sub-Ventricular Zone (SVZ) naturally occurring after ischemia. In order toclarify the role of the SVZ neurogenesis in animal recovery, the effect ofneurogenesis inhibition and boosting were studied in the mouse MiddleCerebral Artery occlusion model (MCAo). 6 to 10-week-old male micewere pre-treated with intracranial injections of lentiviral vector (LV) orintegration deficient lentiviral vectors (IDLV), in order to target the SVZ.The IDLV carried an expression cassette encoding for a precursor Glialcell-derived neurotrophic factor (GDNF) or the tetanus toxin fragment C(TTC), which recently has been demonstrated to have growth factor likebehaviour. Another group of animals received the LV carrying a doublepromoter expression cassette encoding for an eGFP, and in order to inhibitthe cell cycle in targeted cells the shRNA_Cyclin D1. All vectors wereco-injected with the LV_ pHR’SIN-cPPT-SEW, which contains an eGFPcassette. Two weeks later the animals received the MCAo, and for threeweeks the sensorimotor behaviour was tested. Neurological assessmentshowed the sensory-motor debilitation was significant increased after thetreatment with the LV_shRNA_CyclinD1 (* p<0.05); the IDLV_GDNFand IDLV_TTC groups showed a trend to improve neurological deficit inthe subjects alive until day 5. In the IDLV_GDNF, the SVZ’s derivedgreen cells were positively correlated with the ischemic volume, *p<0.05R=0.68, and the neurodegeneration, ***p<0.001 R=0.92. Moreover, whilethe SVZ neurogenesis inhibition reduced life expectancy, the boostingsignificantly improved it. Immunofluorescence analysis showed amigration extended to the striatum and cortex with a max distance of 1.87mm from the SVZ.

M3 - Doctoral Thesis

ER -