Different Mechanisms of Secondary Neuronal Damage in Thalamic Nuclei After Focal Cerebral Ischemia in Rats

Abstract

Background and Purpose-After focal cerebral ischemia, depending on its localization and extent, secondary neuronal damage may occur that is remote from the initial lesion. In this study differences in secondary damage of the ventroposterior thalamic nucleus (VPN) and the reticular thalamic nucleus (RTN) were investigated with the use of different ischemia models. Methods-Transient middle cerebral artery occlusion (MCAO) leads to cortical infarction, including parts of the basal ganglia such as the globus pallidus, and to widespread edema. Photothrombotic ischemia generates pure cortical infarcts sparing the basal ganglia and with only minor edema. Neuronal degeneration was quantified within the ipsilateral RTN and VPN 14 days after ischemia. Glial reactions were studied with the use of immunohistochemistry. Results-MCAO resulted in delayed neuronal cell loss of the ipsilateral VPN and RTN. Glial activation occurred in both nuclei beginning after 24 hours. Photothrombotic ischemia resulted in delayed neuronal cell loss only within the VPN. Even 2 weeks after photothrombotic ischemia, glial activation could only be seen within the VPN. Conclusions-Pure cortical infarcts after photothrombotic ischemia, without major edema and without effects on the globus pallidus of the basal ganglia, only lead to secondary VPN damage that is possibly due to retrograde degeneration. MCAO, which results in infarction of cortex and globus pallidus and which causes widespread edema, leads to secondary damage in the VPN and RTN. Thus, additional RTN damage may be due to loss of protective GABAergic input from the globus pallidus to the RTN or due to the extensive edema. Retrograde degeneration is not possible because the RTN, in contrast to the VPN, has no efferents to the cortex.

Stimulation of autophagy by rapamycin protects neurons from remote degeneration after acute focal brain damage

“…Conversely, the function of autophagy in acute brain damage remains unknown. 16,17 Functional impairments after acute brain damage are associated with axonal lesions in common pathologies, such as multiple sclerosis, 18 stroke, 19 and spinal and brain trauma. 20 In addition to interrupting the flow of information, axonal damage affects the parent neuronal cell bodies in regions that are remote but functionally connected to the primary lesion.…”

Longitudinal Diffusion Changes in Cerebral Hemispheres after MCA Infarcts

“…These secondary degenerative processes are usually detected within the ipsilateral hemisphere to the lesion. Neuronal degeneration has been particularly detected within the ipsilateral thalamus and the substantia nigra both in rats and in humans after middle cerebral artery (MCA) occlusion (Dihne et al, 2002;Ogawa et al, 1997a, b;Tamura et al, 1990). Together, the ischemic lesion and these remote degenerative processes can lead to a progressive atrophy of the hemisphere ipsilateral to the lesion (Persson et al, 1989;Skriver et al, 1990).…”

Neurologic and Pregnancy Effects of Carbon Monoxide Exposure

“…Regions with relatively poor vascularization and "watershed" areas between two sources of blood supply, such as the globus pallidus, may be more vulnerable, especially during periods of hypotension [27]. The effects of hypoxia on the brain, therefore, do not reflect the cause and neither the character of the lesions nor the areas affected are regarded as pathognomonic for CO [28].…”