INTRODUCTION:. INTRODUCTION: SCIENTIFIC QUESTIONS: How does astrocyte proliferation affect monocyte invasion? ---- Which are the consequences on scar.

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Presentation transcript:

INTRODUCTION:

SCIENTIFIC QUESTIONS: How does astrocyte proliferation affect monocyte invasion? ---- Which are the consequences on scar formation? ----

Astrocyte localization EXPERIMENTAL DATA: DYNAMICS OF ASTROCYTES PROLIFERATION AND IMMUNE CELL INFILTRATION AFTER CORTEX TRAUMATIC INJURY Astrocyte localization

temporal relation between juxtavascular astrocyte proliferation and immune cell invasion

Identification the nature of the invading CD45+ cells after injury

Astrocyte proliferation influence on invading monocytes LOSS OF FUNCTION: INCREASED NUMBER OF CD45+/Iba1- CELLS IN CEREBRAL CORTEX AFTER STAB WOUND INJURY IN MICE WITH REDUCED PROLIFERATION OF ASTROCYTES. Astrocyte proliferation influence on invading monocytes

REDUCED INFILTRATION OF CCR2+ MONOCYTES INCREASES ASTROCYTE PROLIFERATION Decrease of monocyte invasion

Juxtavascular astrocyte proliferation contribute to restrict monocyte invasion

REDUCED SCAR FORMATION AND IMPROVED NEUROPROTECTION IN THE INJURED GM OF CCR2-/- MICE Long-term consequences of CCR2-/- mice

Analysis of neurons in the lesion site

components of the extracellular matrix as further indicators of the scar formation

Improvements of the cortex persisted into later stages

CONCLUSION: Astrocytes proliferation monocytes Juxtavascular astrocyte proliferation Monocyte invasion Reduced scar formation

Future prospects: genome-wide expression differences between juxta- and non-juxtavascular astrocytes ---- identify the secretome and surface proteome of invading monocytes ---- determine whether the different effects obtained by blocking CCR2+ cell recruitment are due to differential effects on glial cell proliferation ----

Bibliography: Burda J, Bernstein A, Sofroniew M. Astrocyte roles in traumatic brain injury. Exp Neurol. 2016 Jan;275 Pt 3:305-315. ---- McGraw J, Hiebert GW, Steeves JD. Modulating astrogliosis after neurotrauma. J Neurosci Res. 2001 Jan 15;63(2):109-15. ---- Anderson MA, Burda JE, Ren Y, Ao Y, O'Shea TM, Kawaguchi R, Coppola G, Khakh BS, Deming TJ, Sofroniew MV. Astrocyte scar formation aids central nervous system axon regeneration. Nature. 2016 Apr 14;532(7598):195-200. ---- Ransohoff RM, Schafer D, Vincent A, Blachère NE, Bar-Or A. Neuroinflammation: Ways in Which the Immune System Affects the Brain. Neurotherapeutics. 2015 Oct;12(4):896-909. ----