Bilateral one-stage ligation of the common carotid arteries in rats is the most common method of forming prolonged cerebral hypoxia with cognitive impairment. Pharmacological studies are most commonly performed at the early postoperative periods, up to 3 days. They are characterized by neuronal death, hypoenergetic state, and edema. In the acute period (3–8 days), changes are associated with the activation of astrocytes, which form intercellular cooperation between the neuron, hemocapillary, and respiratory burst of neutrophil granulocytes. Thus, the permeability of the blood–brain barrier increases, accompanied by the death of one part of the neurons and the improvement of the vitality of another part. The subacute period (from 8 days to 8 weeks) is accompanied by the death of neurons in a state of poor life support, microglial activation, myelin fiber damage, increased diameter of paravertebral arteries in the early period, and the development of astrocytosis and angiogenesis in the late period, which leads to increased lipid peroxidation, secondary damage, and neuronal death. In the late period, neurodystrophic changes appear, and minor neuronal apoptosis and increased permeability of the blood–brain barrier persist. Surviving neurons show metabolic activation and concentration of pericarions near the hemocapillaries.