CNS injury, 1 laminin, and its KDI peptide

............................................................................................................7 INTRODUCTION .....................................................................................................9 THE VULNERABLE CENTRAL NERVOUS SYSTEM..........................................................................9 REVIEW OF THE LITERATURE...........................................................................11 1. EXTRACELLULAR MATRIX AND THE BASEMENT MEMBRANE............................................11 2. LAMININS ...........................................................................................................................................12 2.1. Nomenclature..................................................................................................................................12 2.2. Structure .........................................................................................................................................13 2.3. Role in CNS development................................................................................................................16 2.4.CNS distribution...............................................................................................................................17 2.5. Migration and axonal growth ...........................................................................................................18 2.6 Fragments, peptides, and their functions............................................................................................19 3. MECHANISMS OF INJURY ..............................................................................22 3.1 Excitotoxicity...................................................................................................................................22 3.2 Trauma.............................................................................................................................................23 3.3 Ischemia...........................................................................................................................................24 3.3.1 Focal brain ischemia .................................................................................................................24 3.3.2 Ischemic brain edema................................................................................................................25 3.4 Kainic acid-induced neurotoxicity.....................................................................................................25 3.5 Inflammation.................................................................................................................................... 26 3.6 Apoptosis .........................................................................................................................................27 4. REGENERATION................................................................................................................................28 4.1 Hampering factors ............................................................................................................................29 4.1.1 Glial scar ..................................................................................................................................29 4.1.2 Myelin inhibition ......................................................................................................................30 4.2 Inducing factors................................................................................................................................30 4.2.1 Neurotrophins ...........................................................................................................................30 4.2.2 Other growth factors .................................................................................................................31 4.2.3 Laminin ....................................................................................................................................32 4.2.4 KDI peptide ..............................................................................................................................33 AIMS OF THE STUDY ..........................................................................................35 MATERIALS AND METHODS ..............................................................................36 RESULTS..............................................................................................................42 1. Effects of KDI peptide in experimental culture systems (Study I) .......................................................42 2. Protection against KA-induced hippocampal damage (Study II) ........................................................42