Focal circumvention of blood-brain barrier with grafts of muscle, skin and autonomic ganglia.

The efficacy with which circulating horseradish peroxidase (HRP) spreads from transplants into the brain's interstitial spaces (IS), was assessed by 3 factors: graft type, site and age. Pieces of skeletal muscle, skin or entire superior cervical ganglion (SCG) were inserted into the IV ventricle (ventricular) or substance of the brain (parenchymal). The age of the grafts, i.e. the intervals after transplantation, were 1, 3, 6 and 12 months. Generally, HRP spread into the IS to about the same extent from ventricular muscle and skin autografts--1 mm, but less from parenchymal SCG allografts--0.5 mm. The spread from all grafts--ventricular and parenchymal--diminished with time. Exudation distance from muscle was the same as that from skin grafts for the first 6 months, but by 1 year, the penetration was significantly greater from muscle than from skin transplants. The flow of HRP was more extensive from parenchymal SCG grafts than from parenchymal muscle and skin grafts at 6 and 12 months. In some of the 6 and 12 month old parenchymal grafts of muscle and skin, no detectable HRP was extravasated. HRP consistently penetrated the brain more deeply from ventricular skin and muscle grafts than from parenchymal ones because more tissue mass survived in ventricular than in parenchymal autografts. Though care was taken not to damage the brain surface during ventricular insertion, there was a consistent, vigorous, collateral sprouting of, as yet unidentified, cranial nerves. These sprouts innervated muscle and skin autografts which, consequently, were able to survive for at least 1 year and contained vessels permeable to HRP. Allografts of muscle between inbred strains did not become innervated, survived for only 2 months and contained the central, barrier type of vessels, but not their intrinsic, permeable type. Thus, it is the muscle cell or its basal lamina within muscle grafts that determines the type of surviving vessel. In SCG allografts, even when all their ganglion cells had disappeared, leaving only connective tissue, Schwann cells and their basal lamina, the ganglion's capillaries survived and remained permeable to HRP. Therefore, the characteristics of the SCG vessels are determined by the Schwann cell-fibroblast milieu rather than the neuronal one.

Muscle grafts as entries for blood-borne proteins into the extracellular space of the brain.

Nuchal muscle autografts of two different sizes were transplanted into rat brain parenchyma (intraparenchymal, 1.5 X 1.5 X 1 mm) and onto the surface of the brain stem (intraventricular, 2 X 2 X 1 and 1.5 X 1.5 X 1 mm). The vasculature of the transplants retained its permeability to proteins. Exogenous, intravenously injected horseradish peroxidase (HRP) and endogenous immunoglobulins (IgG) crossed the vessels of the grafts to enter the surrounding brain tissue 1 and 3 months after transplantation. HRP infiltrated about 0.46 to 4.6 mm into the extracellular spaces around the grafts 60 minutes after its intravenous injection. The penetration of HRP depended on the size and age of the graft. Infiltration was greater in 1-month-old rats with slightly larger intraventricular grafts than in those with smaller grafts. There was a tendency for the penetration of HRP to be greater from 1-month-old grafts than from 3-month-old grafts, but the difference was not statistically significant, except for the horizontal vector of spread in the intraparenchymal group. Although endogenous IgG infiltrated the surrounding brain tissue, its penetration was very limited in comparison with that of HRP. The results suggest that muscle grafts could be used as a readily available and accessible means of circumventing the blood-brain barrier selectively and focally.