Less hippocampal neuronal death in young gerbils following transient global cerebral ischemia is associated with long‑term maintenance of insulin‑like growth factor�1 and its receptors in the hippocampal CA1 region

Abstract

Insulin-like growth factor 1 (IGF-1) is a well-known growth factor with well-defined neuroprotective effects against cerebral ischemia. However, the age-dependent differences in the expression of IGF-1 and its receptor (IGF-1R) in the brain following transient cerebral ischemia (TCI) have not been elucidated. In the present study, the differences in IGF-1 and IGF-1R in the gerbil hippocampal CA1 region of young and adult gerbils 5 min following TCI were determined. Seven days following TCI, the neuronal death in the hippocampal CA1 region of young gerbils was significantly less than that observed in adult gerbils. In addition, the immunoreactivity, and levels of IGF-1 and IGF-1R in the CA1 region of the normal young were higher than those in the normal adult. Four days following TCI, the immunoreactivity, and protein levels of IGF-1 and IGF-1R were markedly decreased in the adult group. By contrast, in the young group, the immunoreactivity and expression levels were much greater than those in the adult group. However, 7 days following TCI, all immunoreactivity and expression levels were markedly decreased when compared with those in the normal adult and young groups. In addition, the immunoreactivity and expression levels in the young groups were significantly higher than those of the adult groups. In conclusion, the present study demonstrated that the higher and sustained expression of IGF-1 and IGF-1R in the young gerbil hippocampal CA1 region following TCI may be associated with the reduced neuronal death compared to that in the adults.

Differences in TNF‑α and TNF‑R1 expression in damaged neurons and activated astrocytes of the hippocampal CA1 region between young and adult gerbils following transient forebrain ischemia

“…In addition, the number of dead pyramidal neurons (DND) at 7 and 15 days after tFI was significantly lower in the young ischemia group than that in the adult ischemia group. This result is consistent with our and other previous studies reporting that tFI-induced DND in the hippocampal CA1 in young gerbils was shown in fewer pyramidal neurons and more delayed in time than that shown in adult gerbils ( 9 , 24 , 25 ). Taken together, we suggest that the difference of DND between young and adult groups might be associated with the differences of various factors to affect DND, including glial activation, inflammatory cytokine expression and NMDA receptor expression ( 26 – 28 ).…”

“…TNF-R1, tumor necrosis factor receptor 1; CA1, cornu ammonis 1; SP, stratum pyramidale; tFI, transient forebrain ischemia; ROD, relative optical density; SO, stratum oriens; SR, stratum radiatum. DND in the hippocampal CA1 in young gerbils was shown in fewer pyramidal neurons and more delayed in time than that shown in adult gerbils (9,24,25). Taken together, we suggest that the difference of DND between young and adult groups might be associated with the differences of various factors to affect DND, including glial activation, inflammatory cytokine expression and NMDA receptor expression (26)(27)(28).…”

“…Following cerebral ischemia, neuroinflammatory responses and upregulation of inflammatory cytokines occurs generally in the brain, and the imbalance between pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, and anti-inflammatory cytokines could lead to the neuronal damage after ischemic injury (2)(3)(4)(5). In addition, the cerebral ischemia-induced neuronal damage has been also known to be affected by various factors, including ischemic duration, the age and sex of experimental animals (6)(7)(8)(9). TNF-α plays a diverse biological role in regulating inflammatory responses, and its biological actions is mediated through two plasma membrane receptors, TNF receptor 1 (TNF-R1) and TNF-R2, which are present in all cell types, including neurons and glial cells, in the CNS (10)(11)(12).…”

“…Following cerebral ischemia, neuroinflammatory responses and upregulation of inflammatory cytokines occurs generally in the brain, and the imbalance between pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, and anti-inflammatory cytokines could lead to the neuronal damage after ischemic injury ( 2 – 5 ). In addition, the cerebral ischemia-induced neuronal damage has been also known to be affected by various factors, including ischemic duration, the age and sex of experimental animals ( 6 – 9 ).…”

A Network-Based Method for Mechanistic Investigation and Neuroprotective Effect on Post-treatment of Senkyunolid-H Against Cerebral Ischemic Stroke in Mouse

“…Protein phosphatase binding is closely related to CIS, for example, the insulin-like growth factor 1 receptor often facilitates cell survival, cell proliferation, metabolism, and stress resistance triggered by the tyrosine autophosphorylation of its β chains (40). In addition, our previous findings indicated that insulin-like growth factor 1 receptor may be an alternative target for preventing the cerebral ischemic injury (41).…”