Transmission routes of HIV-1 gp120 from brain to lymphoid tissues.

The blood-brain barrier (BBB) restricts the entry of antiviral agents into the CNS thereby facilitating the creation of a reservoir of HIV that could potentially reinfect peripheral tissues. We characterized the efflux from brain of radioactively labeled viral coat HIV-1 gp120 (I-gp120) after intracerebroventricular (i.c.v.) injection. The half-time disappearance rate of I-gp120 from brain was 12.6 min, which was faster than could be explained by the reabsorption of cerebrospinal fluid into blood but could not be explained by a saturable transporter. After i.c.v. injection, I-gp120 appeared in the serum and was sequestered by spleen and the cervical nodes, demonstrating a potential for virus within the CNS to reinfect peripheral tissues. However, the amount of I-gp120 appearing in serum was less than that expected based on the efflux rate, whereas uptake by the cervical nodes was much greater after i. c.v. than after i.v. injection of I-gp120. These findings were explained by drainage from the brain directly to the cervical lymph nodes through the brain's primitive lymphatic system. These lymphatics potentially provide a pathway through which CNS reservoirs of HIV-1 could directly reinfect lymphoid tissue without being exposed to circulating antiviral agents.

Sequestration of centrally administered insulin by the brain: effects of starvation, aluminum, and TNF-alpha.

Insulin found in the CNS may be a key regulator in the balance of energy in the body. Since the peripheral circulation is the principal source of insulin in the CNS, insulin must cross the blood-brain barrier. We examined the retention of radioactively labeled insulin in the brain and its transport from the brain after injection icv in mice. The results were compared with those found in mice after fasting, starvation, refeeding, and the addition of aluminum (previously shown to affect the transport of peptides from the CNS) as well as tumor necrosis factor-alpha (TNF-alpha) (known to interact with peripheral insulin). There was no obvious saturable transport system for insulin from the brain, but the retention of insulin was regulated by both aluminum and starvation. Although TNF-alpha was neither required nor involved chronically in the retention of insulin in the brain, acute ip administration of TNF-alpha produced an early increase in the retention of insulin similar to that found after starvation.

Effects of hormonal treatment and history on scopolamine inhibition of lordosis.

The muscarinic receptor blocker, scopolamine, inhibits the display of lordosis behavior in female rats but its effectiveness depends on hormonal conditions. In these experiments, systemic administration of scopolamine (0.031-4 mg/kg) inhibited lordosis in ovariectomized rats brought into receptivity by treatment with a low dose of estradiol benzoate (EB, 0.25 micrograms for 3 days) with progesterone (P, 500 micrograms for 1 day), or a high dose of EB (25 micrograms for 3 days) with and without P. However, the effectiveness of scopolamine was reduced at the high dose of EB and with the addition of P. Furthermore, scopolamine failed to inhibit lordosis in females treated on a second week with the high dose of EB with or without P, unless an interval of at least 3 weeks separated the two sets of steroid treatments. The reduced effectiveness of scopolamine cannot be explained by peripheral mechanisms because its inhibitory effect on lordosis also was reduced following repeated hormonal exposure even when scopolamine was infused directly into the lateral ventricles.