Effects of infantile hydrocephalus and ventriculoperitoneal shunting on afferent and efferent connections of the sensorimotor cortex

Connectivity of the cerebral cortex may be irreversibly altered by hydrocephalus. Previous studies have supported this hypothesis by demonstrating reductions in cortical synapses, decreased monoamine levels, pyknotic neurons in layers V and VI, dendritic atrophy, demyelination and axonal degeneration in periventricular white matter. To examine this possibility directly, a study using an axonal tracer was initiated on kittens in which hydrocephalus was induced at 9-11 days of age by intracisternal injection of kaolin. At 10-14 days post-kaolin, 5 hydrocéphalie animals received low pressure ventriculoperitoneal (VP) shunts. Normal age-matched animals served as controls. Hydrocéphalie and shunted animals were monitored by ultrasound to document progression of hydrocephalus. Injections of horseradish peroxidase conjugated with wheat-germ agglutinm (WGAHRP) were made unilaterally in cortical areas 3, 4 and 6 as follows: hydrocéphalie animals at 9-15 days post-kaolin; shunted animals at 1, 2 and 4 weeks post shunt; control animals at times corresponding to the ages of the hydrocéphalie shunted animals. Tissue from the entire brain was processed by routine HRP histochemistry and analysed using light microscopy. Retrograde labelling in the contralateral somatosensory cortex and ipsilateral thalamus, ventral tegmental area and locus coeruleus was absent or reduced in untreated hydrocéphalie animals, but returned to normal after VP shunting. VP shunting returned retrograde labelling in these areas to normal. Anterograde labelling in the contralateral somatosensory cortex and the ipsilateral thalamus was absent or reduced in untreated hydrocephalic animals. VP shunting increased anterograde labelling in these areas, but not to normal levels. These results suggest that 1) cortical connectivity is impaired in untreated infantile hydrocephalus and involves both afferent and efferent pathways, 2) shunting improves both cortical afferent and efferent connectivity and 3) complete re-establishment of the cortical efferent pathways may not occur. Such changes in cortical pathways, if permanent, could be responsible for many of the motor and cognitive deficits seen clinically in afflicted hydrocéphalie children.