Histological evidence for drug diffusion across the cerebral meninges into the underlying neocortex in rats.
Transmeningeal pharmacotherapy has been proposed to treat neurological disorders with localized pathology, such as intractable focal epilepsy. As a step toward understanding the diffusion and intracortical spread of transmeningeally delivered drugs, the present study used histological methods to determine the extent to which a marker compound, N-methyl-D-aspartate (NMDA), can diffuse into the neocortex through the meninges. Rats were implanted with bilateral parietal cortical epidural cups filled with 50 mM NMDA on the right side and artificial cerebrospinal fluid (ACSF) in the contralateral side. After 24 h, the histological effects of these treatments were evaluated using cresyl violet (Nissl) staining. The epidural NMDA exposure caused neuronal loss that in most animals extended from the pial surface through layer V. The area indicated by this neuronal loss was localized to the neocortical region underlying the epidural cup. These results suggest that NMDA-like, water soluble, small molecules can diffuse through the subdural/subarachnoid space into the underlying neocortex and spread in a limited fashion, close to the meningeal penetration site.
NYU Comprehensive Epilepsy Center, Department of Neurology, NYU School of Medicine, New York, NY 10016, USA. nandor.ludvig@med.nyu.edu
Nandor
N
Ludvig
Lynette G
LG
Sheffield
Hai M
HM
Tang
Shirn L
SL
Baptiste
Orrin
O
Devinsky
Ruben I
RI
Kuzniecky
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004396:Coloring Agents; D004058:Diffusion / Q000187:drug effects; D004824:Epidural Space / Q000187:drug effects / Q000502:physiology; D007202:Indicators and Reagents; D015918:Infusion Pumps, Implantable; D008297:Male; D008578:Meninges / Q000187:drug effects* / Q000502:physiology; D008751:Methylene Blue; D016202:N-Methylaspartate / Q000493:pharmacokinetics*; D019579:Neocortex / Q000187:drug effects* / Q000502:physiology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D009498:Neurotoxins / Q000493:pharmacokinetics*; D051381:Rats; D020318:Rats, Long-Evans; D012995:Solubility / Q000187:drug effects; D013346:Subarachnoid Space / Q000187:drug effects* / Q000502:physiology; D013355:Subdural Space / Q000187:drug effects* / Q000502:physiology
D004396:Coloring Agents; D007202:Indicators and Reagents; D009498:Neurotoxins; D016202:N-Methylaspartate; D008751:Methylene Blue