Selective Neuronal Vulnerability of Human Hippocampal CA1 Neurons: Lesion Evolution, Temporal Course, and Pattern of Hippocampal Damage in Diffusion-Weighted MR Imaging

Abstract

The CA1 (cornu ammonis) region of hippocampus is selectively vulnerable to a variety of metabolic and cytotoxic insults, which is mirrored in a delayed neuronal death of CA1 neurons. The basis and mechanisms of this regional susceptibility of CA1 neurons are poorly understood, and the correlates in human diseases affecting the hippocampus are not clear. Adopting a translational approach, the lesion evolution, temporal course, pattern of diffusion changes, and damage in hippocampal CA1 in acute neurologic disorders were studied using high-resolution magnetic resonance imaging. In patients with hippocampal ischemia (n = 50), limbic encephalitis (n = 30), after status epilepticus (n = 17), and transient global amnesia (n = 53), the CA1 region was selectively affected compared with other CA regions of the hippocampus. CA1 neurons exhibited a maximum decrease of apparent diffusion coefficient (ADC) 48 to 72 hours after the insult, irrespective of the nature of the insult. Hypoxic-ischemic insults led to a significant lower ADC suggesting that the ischemic insult results in a stronger impairment of cellular metabolism. The evolution of diffusion changes show that CA1 diffusion lesions mirror the delayed time course of the pathophysiologic cascade typically observed in animal models. Studying the imaging correlates of hippocampal damage in humans provides valuable insight into the pathophysiology and neurobiology of the hippocampus.

Behavioural and brain ultrastructural changes following the systemic administration of propionic acid in adolescent male rats. Further development of a rodent model of autism

“…is well known (Liang et al, 2013;Medvedeva, Ji, Yin, & Weiss, 2017). The basis of such susceptibility is still obscure but may include genetically determined glutamate-dependent and calcium-mediated mechanisms of neuronal excitability and oxidative stress (Bartsch et al, 2015). Under EM, we detected few dark formless "cells."…”

“…is well known (Liang et al, ; Medvedeva, Ji, Yin, & Weiss, ). The basis of such susceptibility is still obscure but may include genetically determined glutamate‐dependent and calcium‐mediated mechanisms of neuronal excitability and oxidative stress (Bartsch et al, ). Under EM, we detected few dark formless “cells.” Based on the size and ultrastructure of these “cells,” we propose that they should be apoptotic residues of large pyramidal neurons, which are the most populous excitatory cell type in the hippocampus and usually contain the excitatory transmitter glutamate.…”

The structural connectivity of the recurrent transient global amnesia

“…Or it refutes the hypothesis that TGA occurs only in patients with predisrupted memory network. Lastly, as the lesions are restricted to the lateral region of cornu ammonis and typical retention span lasted just a few minutes , the structural disruption is not detected.…”

“…It is presumed that the structural steadiness of recurrent TGA attributes to the preserved cellular energy state and ion homeostasis. Although the cellular metabolic rate fluctuates during TGA attack, the preserved cellular energy and ion homeostasis prevent the necrosis of hippocampal cells . The significantly lesser pronounced diffusion lesion of TGA‐induced changes compared with ischemia‐induced changes suggested the milder impairment of cellular metabolism, leading to a less severe structural changes .…”

Transient hippocampal CA1 lesions in humans impair pattern separation performance

“…Indeed, beyond our own studies (Bartsch et al, , , ), a variety of other studies also observed focal hyperintense MR‐lesions selectively in the area of CA1 thus providing a natural lesion model of CA1 neurons (Sedlaczek et al, ; Weon, Kim, Lee, & Kim, ). The neurons in CA1 are highly vulnerable against metabolic and vascular noxious input (Bartsch et al, ). Typically, lesions outside CA1 or outside the hippocampus are not detected in TGA (Bartsch & Deuschl, ; Bartsch et al, ).…”