Hypoxic–ischemic injury causes functional and structural neurovascular degeneration in the juvenile mouse retina

Abstract

Ischemic stroke is a major cause of long-term disabilities, including vision loss. Neuronal and blood vessel maturation can affect the susceptibility of and outcome after ischemic stroke. Although we recently reported that exposure of neonatal mice to hypoxia–ischemia (HI) severely compromises the integrity of the retinal neurovasculature, it is not known whether juvenile mice are similarly impacted. Here we examined the effect of HI injury in juvenile mice on retinal structure and function, in particular the susceptibility of retinal neurons and blood vessels to HI damage. Our studies demonstrated that the retina suffered from functional and structural injuries, including reduced b-wave, thinning of the inner retinal layers, macroglial remodeling, and deterioration of the vasculature. The degeneration of the retinal vasculature associated with HI resulted in a significant decrease in the numbers of pericytes and endothelial cells as well as an increase in capillary loss. Taken together, these findings suggest a need for juveniles suffering from ischemic stroke to be monitored for changes in retinal functional and structural integrity. Thus, there is an emergent need for developing therapeutic approaches to prevent and reverse retinal neurovascular dysfunction with exposure to ischemic stroke.

Quantify retinal structure in high-altitude residents with and without high altitude polycythemia

“…Hypoxia and hypobaric nature in high-altitude (HA) area could cause pathologic changes in cardiovascular system, respiratory system and nervous system [1]. The retina is one of the most active tissues, hence pathological level of hypoxia may firstly cause functional and structural changes in retina [2][3][4][5][6][7][8]. Hemorrhages, cotton wool spots, and papilledema that occurred during acute exposure to HA environment are known as high-altitude retinopathy (HAR) [9][10][11].…”

The Assessment of Endovascular Therapies in Ischemic Stroke: Management, Problems and Future Approaches

“…In the event of reduced blood flow to the brain, apart from structural degeneration, there is also a functional dysfunction of blood vessels based on reduced Na + /K + -ATPase activity, overload of cells with sodium, calcium [ 57 ], partial depolarization, and loss of membrane potential, resulting in an increased inflow of sodium ions. This, in turn, leads to the penetration of chlorine ions and water inside the cell, causing swelling of neurons [ 58 , 59 ]. Subsequently, a cascade of biochemical processes related to the release of the main excitatory neurotransmitters, i.e., glutamic acid, produced from presynaptic terminals by depolarization of synaptosomes and hindered uptake by hypoxic astrocytes takes place [ 60 ].…”