Exploring the immunological competence of the meninges and bone marrow in neurological diseases

The brains meninges, i.e. the physical layers surrounding the brain (dura
mater, arachnoid mater, and pia mater), as well as the overlaying skull bone
marrow are a rich source of immunological cells and lymphoid tissues. These
layers and tissues are in close connection and rapidly respond to processes
within the brain, esp. in the case of infections, neuro-inflammation, or tumor
growth. We hypothesize that this immune function is disturbed in patients with
a high-grade glioma, one of the most malignant brain tumors. In-depth
characterization and knowledge on the composition of immune and supportive
cells, including blood and lymph vessels, within these tissues can provide
novel leads to develop treatments for neuro-oncological diseases such as
gliomas. This may also result into valuable knowledge and therapy-development
for other neurological diseases, including multiple sclerosis and Alzheimer*s
disease, hemorrhagic neurological diseases such as subarachnoid and (traumatic)
intracranial hemorrhages, central nervous system infections,
medically-intractable epilepsy, and other congenital or acquired neurological
conditions.

Identifying the (immune) cell composition, co-localization, functions, and
alterations as well as blood and lymph vessels reorganisation in the human*s
dura, arachnoid and pia mater, and skull bone marrow in high-grade glioma
patients as compared to non-glioma controls.

Investigator-initiated observational study.

As participants are already subjected to a neurosurgical operation due to their
primary clinical condition, the additional burden of this study is the
collection of additional tissue on top of that required for primary clinical
care. The skull bone marrow will be collected by small biopsies from easily
reachable exposed bone. A sample of dura mater will be collected and replaced
by autologous duraplasty (i.e. pericranium/periosteal layer) as is already a
standard procedure in approximately 50 % of cranial intradural neurosurgical
operations. Pia and arachnoid mater will only be collected if the brain*s
cortex needs to be entered because of deeper-seated intraparenchymal lesions,
and their removal is thus already part of the operative route. From patients of
whom during the operation a duraplasty has to be created, and of whom dura
mater has to be reduced to simplify integration of the duraplasty, the
left-over dura mater is collected for this study (*rest-materiaal*). From this
particular group of patients, skull bone marrow is collected from left-over
bone splinters generated with placing the burr hole for skull trephination, or
from the bone flap when left-out (craniectomy; both *rest-materiaal*). All
material will be collected pseudonymously, and there will be no follow-up
visits. The estimated risk from collecting skull bone marrow, and pia,
arachnoid and dura mater is considered moderate. There are no benefits to the
participants.