Intracerebral Transplants and Memory Dysfunction: Circuitry Repair or Functional Level Setting?

Abstract

Intracerebral grafting techniques of fetal neural cells have been used essentially with two main types of lesion paradigms, namely damage to long projection systems, in which the source and the target are clearly separate, and damage to neurons that are involved in local circuits within a small (sub)region of the brain. With the’first lesion paradigm, grafts placed homotopically (in the source) are not appropriate because their fibers grow poorly through the host parenchyma and fail to reach their normal target. To be successful, the grafts must be placed ectopically in the target region of the damaged projection systems, where generally they work as level-setting systems. Conversely, with the second paradigm, the grafts are supposed to compensate for a local loss of neurons and must be placed homotopically to induce functional effects that are based on the reconstruction of a point-to-point circuitry. By inserting a biological or artificial bridging-substrate between the source and the target of long projection systems, it might be possible to combine the positive effects of both homotopic and ectopic grafting by achieving both target reinnervation and normal control of the grafted neurons within the source area. These issues are illustrated and discussed in this review.

Cognitive dysfunction and depression in Parkinson’s disease: what can be learned from rodent models?

“…, 1998). However, a few preclinical studies have explored cognitive‐related functions in association with neural transplantation in rodents with a striatal lesion, pointing out important keys to a functional recovery (Will et al. , 2000).…”

Does the Regeneration of Hippocampal Neurons Offer Hope for the Treatment of Cognitive Deficits?

“…Although the early findings for regenerating brain circuitry were promising, the long-term results have been unimpressive. There is a lack of evidence for longterm survival of grafted neurons [2,3,5] and for normal functional, synaptic integration into an existing neural network [2,3,6]. In summary, these approaches have generated some limited success.…”

A Novel Animal Model of Hippocampal Cognitive Deficits, Slow Neurodegeneration, and Neuroregeneration

“…Even in instances of excellent graft survival with multiple transplant locations, there are clear persisting functional deficits [ 8 – 10 ]. It seems that normal information processing does not take place in hippocampal grafts [ 8 , 11 ]. There is some recent evidence that grafts of embryonic CA3 tissue promote expression of calbindin in existing hippocampal neurons after CA3 excitotoxic injury, and this might be beneficial for hippocampal excitability [ 12 ].…”