中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (9): 1477-1480.doi: 10.4103/1673-5374.255957

• 综述:脑损伤修复保护与再生 •    下一篇

重塑树突棘用于治疗创伤性脑损伤

  

  • 出版日期:2019-09-15 发布日期:2019-09-15

Remodeling dendritic spines for treatment of traumatic brain injury

Ye Xiong 1 , Asim Mahmood 1 , Michael Chopp 2, 3   

  1. 1 Department of Neurosurgery, Henry Ford Hospital, Detroit, MI, USA
    2 Department of Neurology, Henry Ford Hospital, Detroit, MI, USA
    3 Department of Physics, Oakland University, Rochester, MI, USA
  • Online:2019-09-15 Published:2019-09-15
  • Contact: Ye Xiong, MD, PhD, yxiong1@hfhs.org

摘要:

orcid: 0000-0001-9770-6031 (Ye Xiong)

Abstract:

Traumatic brain injury is an important global public health problem. Traumatic brain injury not only causes neural cell death, but also induces dendritic spine degeneration. Spared neurons from cell death in the injured brain may exhibit dendrite damage, dendritic spine degeneration, mature spine loss, synapse loss, and impairment of activity. Dendritic degeneration and synapse loss may significantly contribute to functional impairments and neurological disorders following traumatic brain injury. Normal function of the nervous system depends on maintenance of the functionally intact synaptic connections between the presynaptic and postsynaptic spines from neurons and their target cells. During synaptic plasticity, the numbers and shapes of dendritic spines undergo dynamic reorganization. Enlargement of spine heads and the formation and stabilization of new spines are associated with long-term potentiation, while spine shrinkage and retraction are associated with long-term depression. Consolidation of memory is associated with remodeling and growth of preexisting synapses and the formation of new synapses. To date, there is no effective treatment to prevent dendritic degeneration and synapse loss. This review outlines the current data related to treatments targeting dendritic spines that propose to enhance spine remodeling and improve functional recovery after traumatic brain injury. The mechanisms underlying proposed beneficial effects of therapy targeting dendritic spines remain elusive, possibly including blocking activation of Cofilin induced by beta amyloid, Ras activation, and inhibition of GSK-3 signaling pathway. Further understanding of the molecular and cellular mechanisms underlying synaptic degeneration/loss following traumatic brain injury will advance the understanding of the pathophysiology induced by traumatic brain injury and may lead to the development of novel treatments for traumatic brain injury.

Key words: traumatic brain injury, dendritic spines, synaptic plasticity, spinogenic agents, treatment, spine remodeling, memory, functional recovery