Trends in Neurosciences
Volume 23, Issue 6, 1 June 2000, Pages 265-271
Journal home page for Trends in Neurosciences

Review
Recovery recapitulates ontogeny

https://doi.org/10.1016/S0166-2236(00)01562-9Get rights and content

Abstract

Several studies support the hypothesis that after stroke, specific features of brain function revert to those seen at an early stage of development, with the subsequent process of recovery recapitulating ontogeny in many ways. Many clinical characteristics of stroke recovery resemble normal development, particularly in the motor system. Consistent with this, brain-mapping studies after an ischemic insult suggest re-emergence of childhood organizational patterns: recovery being associated with a return to adult patterns. Experimental animal studies demonstrate increased levels of developmental proteins, particularly in the area surrounding an infarct, suggesting an active process of reconditioning in response to cerebral ischemia. Understanding the patterns of similarity between normal development and stroke recovery might be of value in its treatment.

Section snippets

Motor performance

For several decades, researchers have described behavioral parallels between the successive stages of normal development and recovery from brain injury. For example, Hines showed that the normal development of locomotion and posture in rhesus monkeys passed through states similar to those seen during stroke recovery4. Teitelbaum et al. found that the four stages of feeding behavior in normal development re-emerged in rats recovering from a lateral hypothalamic injury5. Other studies from his

Bilateral motor control

Childhood is associated with bilateral motor control, in association with immaturity of the corticospinal connections that are essential for fractionated unilateral movements. In contrast, adulthood is associated primarily with contralateral motor control, together with well-developed corticospinal tract size and function10, 11. Muller et al.12 found that transcranial magnetic stimulation of motor cortex induced bilateral responses in hand and arm muscles of most children, but only

Cortical-map plasticity

Brain-mapping studies have supported the idea that in humans, a number of cortical regions contain orderly but overlapping representation of body regions29, 30. In animal studies, these maps show a degree of redundancy and overlap31, a finding also described in human brain-mapping studies32. The capacity to reorganize cortical representational maps might be maximal at early time points in development. For example, hemispherectomy during early childhood can be associated with remapping of motor,

Re-emergence of molecular and cellular developmental events

Developmental proteins normally absent or present at very low levels in adult brain re-emerge after an ischemic brain insult, often at a time of limited cellular metabolic resources. A wide range of proteins have been described, many focused in the penumbral area surrounding an infarct and some appearing in bilateral hemispheres (Fig. 2). Increased proteins levels after stroke are related to changes in the extracellular matrix, glial structure, neuronal growth, apoptosis, angiogenesis and

Clinical approaches

The analogy between development and stroke recovery could suggest clinical approaches to maximize patient outcomes. NMDA-receptor block is a strategy employed in many current therapeutic trials of acute ischemic stroke. However, during development, such inhibition is associated with reduced dendritic and synaptic pruning61, 62, 63. Similarly, during stroke recovery, NMDA-receptor antagonism is also associated with prevention of dendritic pruning and increased behavioral deficits64, 65. Levels

Concluding remarks

In 1866, Haeckel proposed that ontogeny recapitulates phylogeny. Some elements of his theories have been of heuristic value. In recent decades, a number of researchers have recognized parallels that exist between stroke recovery and ontogeny, with examples described at the behavioral, brain mapping, cellular and molecular levels. Animal studies have identified treatments that improve long-term outcome by targeting the events that underlie stroke recovery53, 59, 72, 78. Parallels with

Acknowledgements

The authors thank Denice Bliesath for manuscript preparation. The authors’ research is supported by the NICHHD grant K08 HD1219 (S.C.) and NINDS grants PO1 NS23393 and RO1 NS33627 (M.C.).

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