Tertiary mechanisms of brain damage: a new hope for treatment of cerebral palsy?

TY - JOUR

T1 - Tertiary mechanisms of brain damage

T2 - a new hope for treatment of cerebral palsy?

AU - Fleiss, Bobbi

AU - Gressens, Pierre

PY - 2012/6

Y1 - 2012/6

N2 - Cerebral palsy is caused by injury or developmental disturbances to the immature brain and leads to substantial motor, cognitive, and learning deficits. In addition to developmental disruption associated with the initial insult to the immature brain, injury processes can persist for many months or years. We suggest that these tertiary mechanisms of damage might include persistent inflammation and epigenetic changes. We propose that these processes are implicit in prevention of endogenous repair and regeneration and predispose patients to development of future cognitive dysfunction and sensitisation to further injury. We suggest that treatment of tertiary mechanisms of damage might be possible by various means, including preventing the repressive effects of microglia and astrocyte over-activation, recapitulating developmentally permissive epigenetic conditions, and using cell therapies to stimulate repair and regeneration Recognition of tertiary mechanisms of damage might be the first step in a complex translational task to tailor safe and effective therapies that can be used to treat the already developmentally disrupted brain long after an insult.

AB - Cerebral palsy is caused by injury or developmental disturbances to the immature brain and leads to substantial motor, cognitive, and learning deficits. In addition to developmental disruption associated with the initial insult to the immature brain, injury processes can persist for many months or years. We suggest that these tertiary mechanisms of damage might include persistent inflammation and epigenetic changes. We propose that these processes are implicit in prevention of endogenous repair and regeneration and predispose patients to development of future cognitive dysfunction and sensitisation to further injury. We suggest that treatment of tertiary mechanisms of damage might be possible by various means, including preventing the repressive effects of microglia and astrocyte over-activation, recapitulating developmentally permissive epigenetic conditions, and using cell therapies to stimulate repair and regeneration Recognition of tertiary mechanisms of damage might be the first step in a complex translational task to tailor safe and effective therapies that can be used to treat the already developmentally disrupted brain long after an insult.

KW - CELL-DEATH

KW - WHITE-MATTER

KW - THERAPEUTIC WINDOW

KW - HYPOXIA-ISCHEMIA

KW - LONG-TERM

KW - TRANSIENT FOREBRAIN ISCHEMIA

KW - ADULT HIPPOCAMPAL NEUROGENESIS

KW - CENTRAL-NERVOUS-SYSTEM

KW - HISTONE DEACETYLASE INHIBITION

KW - OLIGODENDROCYTE PROGENITOR MATURATION

U2 - 10.1016/S1474-4422(12)70058-3

DO - 10.1016/S1474-4422(12)70058-3

M3 - Literature review

SN - 1474-4422

VL - 11

SP - 556

EP - 566

JO - Lancet Neurology

JF - Lancet Neurology

IS - 6

ER -