Nonsaturable entry of neuropeptide Y into brain.

Neuropeptide Y (NPY) is found and is active both in the periphery and brain, but its crossing of the blood-brain barrier (BBB) in either direction has not been measured. We used multiple time-regression analysis to determine that radioactively labeled NPY injected intravenously entered the brain much faster than albumin, with an influx constant of 2.0 x 10(-4) ml.

Fate of leptin after intracerebroventricular injection into the mouse brain.

The fate of the metabolic regulatory protein leptin was studied after intracerebroventricular (i.c.v.

Diurnal uptake of circulating interleukin-1alpha by brain, spinal cord, testis and muscle.

The effects, synthesis, and release of cytokines show diurnal patterns. We used recombinant human interleukin-1alpha radioactively labeled with 125I (I-IL) to determine whether its uptake by brain, spinal cord, testis and muscle showed a diurnal rhythm when tested every 4 h in mice. Each tissue showed statistically significant diurnal variation in their uptakes of I-IL ranging from a nearly 10-fold difference for the spinal cord to less than a 2-fold difference for muscle.

Relative contributions of a CVO and the microvascular bed to delivery of blood-borne IL-1alpha to the brain.

Diffusion from brain regions lacking a blood-brain barrier (BBB) and saturable transport across capillaries are possible pathways for the entry of blood-borne interleukin-1alpha into the central nervous system (CNS). To assess the involvement of these putative routes, mice received intravenous injections of radioiodinated interleukin-1alpha, and their brains were subjected to emulsion autoradiography. The resulting patterns of silver grain distribution showed that diffusion of interleukin-1alpha from the choroid plexus and the subfornical organ was greatly restricted.

Differential permeability of the blood-brain barrier to two pancreatic peptides: insulin and amylin.

Insulin and amylin are cosecreted by pancreatic B cells and have receptors within the central nervous system (CNS), where they exert multiple effects. Although these peptides are not produced in the CNS, their ability to cross the blood-brain barrier (BBB) explains their presence there. We used multiple-time regression analysis to measure, in mice, the unidirectional influx constant (Ki) of each of these peptides to compare their rates of transport with each other and in different regions of the brain.

Regional differences in the metabolism of Tyr-MIF-1 and Tyr-W-MIF-1 by rat brain mitochondria.

Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) and Tyr-W-MIF-1 (Tyr-Pro-Trp-Gly-NH2) are endogenous neuropeptides with opiate modulating and other CNS effects. After incubation of the tritiated tetrapeptides with fractions of tissue from different areas of rat brain, formation of the metabolites was determined by HPLC. Marked regional differences in degradation were found for both peptides.

Blood-brain barrier permeability to ebiratide and TNF in acute spinal cord injury.

Spinal cord injury (SCI) in mammals has a poor outcome because of a lack of regeneration. Alteration of the local environment after injury may induce regeneration. However, the passage of blood-borne or exogenous neurotrophic substances through the blood-brain barrier (BBB) is not well characterized in either normal or injured states.

The role of the blood-brain barrier transporter PTS-1 in regulating concentrations of methionine enkephalin in blood and brain.

Previous studies have suggested that peptide transport system (PTS)-1, a saturable efflux system from brain to blood, regulates the concentration in the brain of methionine enkephalin (Met-Enk), an opiate peptide related to the drinking of ethanol in mice. We determined the relationship of PTS-1 to concentrations of immunoreactive Met-Enk in plasma and whole brain in eight randomly selected strains of mice. An active PTS-1 system could be demonstrated in five of the eight strains.

Acute modulation of active carrier-mediated brain-to-blood transport of corticotropin-releasing hormone.

The unidirectional brain-to-blood transport system for corticotropin-releasing hormone (CRH) across the blood-brain barrier could be instrumental in the homeostasis of central CRH. To characterize this system, the intracerebroventricular injection of 125I-CRH was used in mice. CRH was rapidly transported out of the brain with a half-time disappearance (t1/2) of 15 min, much faster than albumin (t1/2 = 50 min).

Reversible association of the cytokines MIP-1 alpha and MIP-1 beta with the endothelia of the blood-brain barrier.

Macrophage inflammatory proteins (MIP)-1 alpha and -1 beta have been postulated to exert their pyrogenic effects by acting directly at sites within the brain. Such activity would require circulating MIP-1s to cross the blood-brain barrier (BBB). We examined the ability of the monomer and polymer of MIP-1 alpha and the polymer of MIP-1 beta radioactively labeled with 125iodine (I-MIP-1) to cross the BBB.

Passage of cytokines across the blood-brain barrier.

One mechanism by which blood-borne cytokines might affect the function of the central nervous system (CNS) is by crossing the blood-brain barrier (BBB) for direct interaction with CNS tissue. Saturable transport systems from blood to the CNS have been described for interleukin (IL)-1 alpha, IL-1 beta, IL-1 receptor antagonist (IL-1ra), IL-6, and tumor necrosis factor-alpha (TNF-alpha). Blood-borne cytokines have been shown to cross the BBB to enter cerebrospinal fluid and interstitial fluid spaces of the brain and spinal cord.